Trial Outcomes & Findings for Efficacy Study of Different Laboratory Management Strategies and Drug Regimens in HIV-infected Children in Africa (NCT NCT02028676)
NCT ID: NCT02028676
Last Updated: 2014-06-06
Results Overview
Number of participants with disease progression to a new WHO stage 4 event or death, to be analysed using time-to-event methods
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1206 participants
Primary outcome timeframe
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
Results posted on
2014-06-06
Participant Flow
All recruited children (n=1206) were randomly assigned to CDM vs LCM and the three different induction ART strategies at enrolment (3/2007-11/2008). This was a factorial randomisation meaning that the children were effectively randomized into 6 parallel groups. Baseline characteristics are presented below separately for each initial randomization.
There were two additional nested substudy randomizations after initial trial enrolment (see inclusion/exclusion criteria for eligibility). From 8/2009 to 6/2010, eligible children were randomized to once vs twice daily abacavir+lamivudine. From 9/2009 to 2/2011, eligible children were randomized to stop vs continue cotrimoxazole prophylaxis.
Participant milestones
| Measure |
Clinically Driven Monitoring (CDM)
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI-\>ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI-\>ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Once-daily ABC+3TC
ABC \[abacavir\]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
|
Twice-daily ABC+3TC
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Twice-daily ABC+3TC
|
Continued Cotrimoxazole Prophylaxis
Once-daily doses 5-\<15 kg: 200 mg of trimethoprim + 40 mg sulfamethoxazole 15-\<30 kg: 400 mg trimethoprim + 80 mg sulfamethoxazole \>=30 kg: 800 mg trimethoprim + 160 mg sulfamethoxazole
Continued cotrimoxazole prophylaxis
|
Stopped Cotrimoxazole Prophylaxis
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
|
|---|---|---|---|---|---|---|---|---|---|
|
Initial Enrolment: CDM vs LCM
STARTED
|
606
|
600
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Initial Enrolment: CDM vs LCM
COMPLETED
|
606
|
600
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Initial Enrolment: CDM vs LCM
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Initial Enrolment: Induction ART
STARTED
|
0
|
0
|
397
|
404
|
405
|
0
|
0
|
0
|
0
|
|
Initial Enrolment: Induction ART
COMPLETED
|
0
|
0
|
397
|
404
|
405
|
0
|
0
|
0
|
0
|
|
Initial Enrolment: Induction ART
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Subsequent Once vs Twice Daily ABC+3TC
STARTED
|
0
|
0
|
0
|
0
|
0
|
336
|
333
|
0
|
0
|
|
Subsequent Once vs Twice Daily ABC+3TC
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
336
|
333
|
0
|
0
|
|
Subsequent Once vs Twice Daily ABC+3TC
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Subsequent Cotrimoxazole Randomization
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
376
|
382
|
|
Subsequent Cotrimoxazole Randomization
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
376
|
382
|
|
Subsequent Cotrimoxazole Randomization
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy Study of Different Laboratory Management Strategies and Drug Regimens in HIV-infected Children in Africa
Baseline characteristics by cohort
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
n=397 Participants
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI-\>ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI-\>ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Once-daily ABC+3TC
n=336 Participants
ABC \[abacavir\]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
|
Twice-daily ABC+3TC
n=333 Participants
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Twice-daily ABC+3TC
|
Continued Cotrimoxazole Prophylaxis
n=376 Participants
Once-daily doses 5-\<15 kg: 200 mg of trimethoprim + 40 mg sulfamethoxazole 15-\<30 kg: 400 mg trimethoprim + 80 mg sulfamethoxazole \>=30 kg: 800 mg trimethoprim + 160 mg sulfamethoxazole
Continued cotrimoxazole prophylaxis
|
Stopped Cotrimoxazole Prophylaxis
n=382 Participants
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
|
Total
n=3839 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
5.9 years
n=5 Participants
|
6.0 years
n=7 Participants
|
NA years
n=5 Participants
|
NA years
n=4 Participants
|
NA years
n=21 Participants
|
NA years
n=10 Participants
|
NA years
n=115 Participants
|
NA years
n=24 Participants
|
NA years
n=42 Participants
|
6.0 years
n=42 Participants
|
|
Age, Customized
< 3 years
|
197 participants
n=5 Participants
|
173 participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, Customized
3 years or older
|
409 participants
n=5 Participants
|
427 participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Sex: Female, Male
Female
|
308 Participants
n=5 Participants
|
302 Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
NA Participants
n=4 Participants
|
NA Participants
n=21 Participants
|
NA Participants
n=10 Participants
|
NA Participants
n=115 Participants
|
NA Participants
n=24 Participants
|
NA Participants
n=42 Participants
|
NA Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
298 Participants
n=5 Participants
|
298 Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
NA Participants
n=4 Participants
|
NA Participants
n=21 Participants
|
NA Participants
n=10 Participants
|
NA Participants
n=115 Participants
|
NA Participants
n=24 Participants
|
NA Participants
n=42 Participants
|
NA Participants
n=42 Participants
|
|
Region of Enrollment
Uganda
|
405 participants
n=5 Participants
|
401 participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment
Zimbabwe
|
201 participants
n=5 Participants
|
199 participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, continuous: Period 2 (trial enrollment, induction ART)
|
NA years
n=5 Participants
|
NA years
n=7 Participants
|
6.1 years
n=5 Participants
|
6.2 years
n=4 Participants
|
5.7 years
n=21 Participants
|
NA years
n=10 Participants
|
NA years
n=115 Participants
|
NA years
n=24 Participants
|
NA years
n=42 Participants
|
6.0 years
n=42 Participants
|
|
Age, continuous: Period 3 (randomization to once vs twice daily ABC+3TC)
|
NA years
n=5 Participants
|
NA years
n=7 Participants
|
NA years
n=5 Participants
|
NA years
n=4 Participants
|
NA years
n=21 Participants
|
5.9 years
n=10 Participants
|
5.1 years
n=115 Participants
|
NA years
n=24 Participants
|
NA years
n=42 Participants
|
5.5 years
n=42 Participants
|
|
Age, continuous: Period 4 (randomization to stop versus continue cotrimoxazole)
|
NA years
n=5 Participants
|
NA years
n=7 Participants
|
NA years
n=5 Participants
|
NA years
n=4 Participants
|
NA years
n=21 Participants
|
NA years
n=10 Participants
|
NA years
n=115 Participants
|
7.5 years
n=24 Participants
|
8.3 years
n=42 Participants
|
7.9 years
n=42 Participants
|
|
Age, categorical: Period 2 (trial enrollment, induction ART)
<3 years
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
121 participants
n=5 Participants
|
117 participants
n=4 Participants
|
132 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, categorical: Period 2 (trial enrollment, induction ART)
3 years or older
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
276 participants
n=5 Participants
|
287 participants
n=4 Participants
|
273 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, categorical: Period 3 (randomization to once vs twice daily ABC+3TC)
<3 years
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
36 participants
n=10 Participants
|
38 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, categorical: Period 3 (randomization to once vs twice daily ABC+3TC)
3 years and older
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
300 participants
n=10 Participants
|
295 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, categorical: Period 4 (randomization to stop versus continue cotrimoxazole)
<3 years
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
0 participants
n=24 Participants
|
0 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Age, categorical: Period 4 (randomization to stop versus continue cotrimoxazole)
3 years and older
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
376 participants
n=24 Participants
|
382 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 2 (trial enrollment, induction ART)
Female
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
204 participants
n=5 Participants
|
197 participants
n=4 Participants
|
209 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 2 (trial enrollment, induction ART)
Male
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
193 participants
n=5 Participants
|
207 participants
n=4 Participants
|
196 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 3 (randomization to once vs twice daily ABC+3TC)
Female
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
173 participants
n=10 Participants
|
172 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 3 (randomization to once vs twice daily ABC+3TC)
Male
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
163 participants
n=10 Participants
|
161 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 4 (randomization to stop versus continue cotrimoxazole)
Female
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
195 participants
n=24 Participants
|
203 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Gender, Male/Female: Period 4 (randomization to stop versus continue cotrimoxazole)
Male
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
181 participants
n=24 Participants
|
179 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 2 (trial enrollment, induction ART)
Uganda
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
266 participants
n=5 Participants
|
268 participants
n=4 Participants
|
272 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 2 (trial enrollment, induction ART)
Zimbabwe
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
131 participants
n=5 Participants
|
136 participants
n=4 Participants
|
133 participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 3 (randomization to once vs twice daily ABC+3TC)
Uganda
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
249 participants
n=10 Participants
|
246 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 3 (randomization to once vs twice daily ABC+3TC)
Zimbabwe
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
87 participants
n=10 Participants
|
87 participants
n=115 Participants
|
NA participants
n=24 Participants
|
NA participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 4 (randomization to stop versus continue cotrimoxazole)
Uganda
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
283 participants
n=24 Participants
|
286 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
Region of Enrollment: Period 4 (randomization to stop versus continue cotrimoxazole)
Zimbabwe
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
NA participants
n=5 Participants
|
NA participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=10 Participants
|
NA participants
n=115 Participants
|
93 participants
n=24 Participants
|
96 participants
n=42 Participants
|
NA participants
n=42 Participants
|
|
CD4 T cell percentage
|
12.5 percentage of total lymphocytes
n=5 Participants
|
12.0 percentage of total lymphocytes
n=7 Participants
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=4 Participants
|
NA percentage of total lymphocytes
n=21 Participants
|
NA percentage of total lymphocytes
n=10 Participants
|
NA percentage of total lymphocytes
n=115 Participants
|
NA percentage of total lymphocytes
n=24 Participants
|
NA percentage of total lymphocytes
n=42 Participants
|
12.0 percentage of total lymphocytes
n=42 Participants
|
|
CD4 T cell percentage: Period 2 (trial enrollment, induction ART)
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=7 Participants
|
11.7 percentage of total lymphocytes
n=5 Participants
|
12.0 percentage of total lymphocytes
n=4 Participants
|
12.5 percentage of total lymphocytes
n=21 Participants
|
NA percentage of total lymphocytes
n=10 Participants
|
NA percentage of total lymphocytes
n=115 Participants
|
NA percentage of total lymphocytes
n=24 Participants
|
NA percentage of total lymphocytes
n=42 Participants
|
12.0 percentage of total lymphocytes
n=42 Participants
|
|
CD4 T cell percentage: Period 3 (randomization to once vs twice daily ABC+3TC)
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=7 Participants
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=4 Participants
|
NA percentage of total lymphocytes
n=21 Participants
|
33.0 percentage of total lymphocytes
n=10 Participants
|
33.0 percentage of total lymphocytes
n=115 Participants
|
NA percentage of total lymphocytes
n=24 Participants
|
NA percentage of total lymphocytes
n=42 Participants
|
33.0 percentage of total lymphocytes
n=42 Participants
|
|
CD4 T cell percentage: Period 4 (randomization to stop versus continue cotrimoxazole)
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=7 Participants
|
NA percentage of total lymphocytes
n=5 Participants
|
NA percentage of total lymphocytes
n=4 Participants
|
NA percentage of total lymphocytes
n=21 Participants
|
NA percentage of total lymphocytes
n=10 Participants
|
NA percentage of total lymphocytes
n=115 Participants
|
33.0 percentage of total lymphocytes
n=24 Participants
|
32.0 percentage of total lymphocytes
n=42 Participants
|
33.0 percentage of total lymphocytes
n=42 Participants
|
|
Duration of antiretroviral therapy: Period 3 (randomization to once vs twice daily ABC+3TC)
|
NA years
n=5 Participants
|
NA years
n=7 Participants
|
NA years
n=5 Participants
|
NA years
n=4 Participants
|
NA years
n=21 Participants
|
1.8 years
n=10 Participants
|
1.8 years
n=115 Participants
|
NA years
n=24 Participants
|
NA years
n=42 Participants
|
1.8 years
n=42 Participants
|
|
Duration of antiretroviral therapy: Period 4 (randomization to stop versus continue cotrimoxazole)
|
NA years
n=5 Participants
|
NA years
n=7 Participants
|
NA years
n=5 Participants
|
NA years
n=4 Participants
|
NA years
n=21 Participants
|
NA years
n=10 Participants
|
NA years
n=115 Participants
|
2.1 years
n=24 Participants
|
2.1 years
n=42 Participants
|
2.1 years
n=42 Participants
|
|
Weight-for-age Z-score: Period 1 (trial enrollment, CDM vs LCM)
|
-2.3 Z-score
n=5 Participants
|
-2.2 Z-score
n=7 Participants
|
NA Z-score
n=5 Participants
|
NA Z-score
n=4 Participants
|
NA Z-score
n=21 Participants
|
NA Z-score
n=10 Participants
|
NA Z-score
n=115 Participants
|
NA Z-score
n=24 Participants
|
NA Z-score
n=42 Participants
|
-2.2 Z-score
n=42 Participants
|
|
Weight-for-age Z-score: Period 2 (trial enrollment, induction ART)
|
NA Z-score
n=5 Participants
|
NA Z-score
n=7 Participants
|
-2.3 Z-score
n=5 Participants
|
-2.2 Z-score
n=4 Participants
|
-2.2 Z-score
n=21 Participants
|
NA Z-score
n=10 Participants
|
NA Z-score
n=115 Participants
|
NA Z-score
n=24 Participants
|
NA Z-score
n=42 Participants
|
-2.2 Z-score
n=42 Participants
|
|
Weight-for-age Z-score: Period 3 (randomization to once vs twice daily ABC+3TC)
|
NA Z-score
n=5 Participants
|
NA Z-score
n=7 Participants
|
NA Z-score
n=5 Participants
|
NA Z-score
n=4 Participants
|
NA Z-score
n=21 Participants
|
-1.4 Z-score
n=10 Participants
|
-1.3 Z-score
n=115 Participants
|
NA Z-score
n=24 Participants
|
NA Z-score
n=42 Participants
|
-1.4 Z-score
n=42 Participants
|
|
Weight-for-age Z-score: Period 4 (randomization to stop versus continue cotrimoxazole)
|
NA Z-score
n=5 Participants
|
NA Z-score
n=7 Participants
|
NA Z-score
n=5 Participants
|
NA Z-score
n=4 Participants
|
NA Z-score
n=21 Participants
|
NA Z-score
n=10 Participants
|
NA Z-score
n=115 Participants
|
-1.3 Z-score
n=24 Participants
|
-1.3 Z-score
n=42 Participants
|
-1.3 Z-score
n=42 Participants
|
PRIMARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Population: All randomized participants (time-to-event)
Number of participants with disease progression to a new WHO stage 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM: Disease Progression to a New WHO Stage 4 Event or Death
|
47 participants
|
39 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new Grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
|
283 participants
|
282 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, 72 weeksPopulation: All participants alive at 72 weeks with CD4 measured (completeness in those in follow-up was 96.6%).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=374 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=388 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=374 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Induction ART: Change From Baseline in CD4% 72 Weeks After ART Initiation
|
16.4 percentage of total lymphocytes
Standard Error 0.45
|
17.1 percentage of total lymphocytes
Standard Error 0.43
|
17.3 percentage of total lymphocytes
Standard Error 0.41
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, 144 weeksPopulation: All participants alive in follow-up with CD4% (95% completeness)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=371 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=387 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=378 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Induction ART: Change From Baseline in CD4% to 144 Weeks From ART Initiation
|
19.8 percentage of total lymphocytes
Standard Error 0.44
|
19.6 percentage of total lymphocytes
Standard Error 0.49
|
19.2 percentage of total lymphocytes
Standard Error 0.46
|
—
|
—
|
PRIMARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=397 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=404 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Induction ART: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
|
157 participants
|
190 participants
|
218 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: 48 weeksPopulation: All randomized participants with VL result from stored plasma specimen (available for 661/669, 99%, randomized participants)
Number of participants with HIV RNA viral load \<80 copies/ml at 48 weeks. Measured retrospectively on stored plasma specimens: due to low stored volumes from some children, samples had to be diluted and therefore a threshold of \<80 copies/ml was used to indicate suppression.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=330 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=331 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Suppressed HIV RNA Viral Load 48 Weeks After Randomisation
|
236 participants
|
242 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, judged definitely/probably or uncertain whether related to lamivudine or abacavir, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV, Judged Definitely/Probably or Uncertain Whether Related to Lamivudine or Abacavir
|
1 participants
|
0 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new hospitalisation or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New Hospitalisation or Death
|
48 participants
|
72 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
|
55 participants
|
64 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants who died from any cause, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: All-cause Mortality
|
25 participants
|
29 participants
|
20 participants
|
14 participants
|
20 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=397 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=404 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Induction ART: New WHO Stage 4 Event or Death
|
30 participants
|
28 participants
|
28 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: New WHO Stage 3 or 4 Event or Death
|
77 participants
|
73 participants
|
73 participants
|
61 participants
|
54 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new or recurrent WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: New or Recurrent WHO Stage 3 or 4 Event or Death
|
91 participants
|
79 participants
|
64 participants
|
53 participants
|
53 participants
|
SECONDARY outcome
Timeframe: Baseline and a median of 4 years (maximum 5 years)Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Weight-for-age Z-score
|
0.76 age-adjusted z-score
Standard Deviation 1.05
|
0.78 age-adjusted z-score
Standard Deviation 1.01
|
0.72 age-adjusted z-score
Standard Deviation 0.95
|
0.79 age-adjusted z-score
Standard Deviation 1.00
|
0.80 age-adjusted z-score
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: Baseline and a median of 4 years (maximum 5 years)Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Height-for-age Z-score
|
0.36 age-adjusted z-score
Standard Deviation 0.65
|
0.43 age-adjusted z-score
Standard Deviation 0.66
|
0.40 age-adjusted z-score
Standard Deviation 0.67
|
0.40 age-adjusted z-score
Standard Deviation 0.65
|
0.38 age-adjusted z-score
Standard Deviation 0.64
|
SECONDARY outcome
Timeframe: Baseline and a median of 4 years (maximum 5 years)Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Body Mass Index-for-age Z-score
|
0.65 age-adjusted z-score
Standard Deviation 1.28
|
0.61 age-adjusted z-score
Standard Deviation 1.20
|
0.56 age-adjusted z-score
Standard Deviation 1.11
|
0.64 age-adjusted z-score
Standard Deviation 1.21
|
0.69 age-adjusted z-score
Standard Deviation 1.39
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants alive in follow-up with CD4% (97% completeness)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=577 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=563 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM: Change From Baseline in CD4% to Week 72
|
17.2 percentage of total lymphocytes
Standard Error 0.36
|
16.7 percentage of total lymphocytes
Standard Error 0.35
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 144Population: All participants alive in follow-up with CD4% (95% completeness)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=579 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=557 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM: Change From Baseline in CD4% to Week 144
|
19.7 percentage of total lymphocytes
Standard Error 0.38
|
19.4 percentage of total lymphocytes
Standard Error 0.38
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants alive in follow-up with CD4
Estimated in those \>5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=326 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=325 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=208 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=231 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=212 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 72
|
408 absolute cells per mm3
Standard Error 22.2
|
385 absolute cells per mm3
Standard Error 19.8
|
402 absolute cells per mm3
Standard Error 24.7
|
447 absolute cells per mm3
Standard Error 28.5
|
336 absolute cells per mm3
Standard Error 22.5
|
SECONDARY outcome
Timeframe: Baseline, week 144Population: All participants alive in follow-up with CD4
Estimated in those \>5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=326 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=320 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=201 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=231 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=214 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 144
|
418 absolute cells per mm3
Standard Error 20.8
|
420 absolute cells per mm3
Standard Error 22.5
|
446 absolute cells per mm3
Standard Error 25.3
|
450 absolute cells per mm3
Standard Error 28.9
|
360 absolute cells per mm3
Standard Error 24.0
|
SECONDARY outcome
Timeframe: 72 weeksPopulation: Viral loads were assayed retrospectively in a random subset of children
Number of participants with HIV RNA viral load \<80 copies/ml 72 weeks after baseline. Threshold for suppression \<80 copies/ml as samples had to be diluted due to low volumes.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=98 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=102 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=73 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=85 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=42 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 72 Weeks After Baseline
|
76 participants
|
78 participants
|
56 participants
|
72 participants
|
26 participants
|
SECONDARY outcome
Timeframe: 144 weeksPopulation: Viral load was assayed retrospectively at week 144 on a random subset of participants, plus all those aged \<5 years at enrolment
Number of participants with HIV RNA viral load \<80 copies/ml 144 weeks after baseline. Threshold for suppression \<80 copies/ml as samples had to be diluted due to low volumes.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=284 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=266 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=168 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=180 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=203 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 144 Weeks After Baseline
|
192 participants
|
193 participants
|
127 participants
|
135 participants
|
124 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants stopping their first-line regimen for clinical/immunological failure, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Cessation of First-line Regimen for Clinical/Immunological Failure
|
28 participants
|
35 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new grade 3 or 4 adverse event definitely/probably or uncertainly related to ART, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: New Grade 3 or 4 Adverse Event Definitely/Probably or Uncertainly Related to ART
|
30 participants
|
42 participants
|
14 participants
|
30 participants
|
28 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new serious adverse events not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: New Serious Adverse Events Not Solely Related to HIV
|
147 participants
|
117 participants
|
87 participants
|
82 participants
|
95 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Number of participants with a new ART-modifying adverse event, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: New ART-modifying Adverse Event
|
31 participants
|
32 participants
|
8 participants
|
30 participants
|
25 participants
|
SECONDARY outcome
Timeframe: Median 4 years (from randomization to 16 March 2012; maximum 5 years)Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=606 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=397 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 Participants
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
LCM vs CDM, Induction ART: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
|
8.5 % of visits reporting missed pills
Standard Deviation 11.1
|
9.4 % of visits reporting missed pills
Standard Deviation 12.4
|
8.3 % of visits reporting missed pills
Standard Deviation 10.8
|
9.5 % of visits reporting missed pills
Standard Deviation 11.8
|
9.1 % of visits reporting missed pills
Standard Deviation 12.7
|
SECONDARY outcome
Timeframe: 96 weeksPopulation: All participants with viral load assayed in stored specimens (98% of those randomized)
Number of participants with HIV RNA viral load \<80 copies/ml at 96 weeks. Threshold for suppression \<80 copies/ml as samples had to be diluted due to low volumes.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=331 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=326 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Suppression of HIV RNA Viral Load 96 Weeks After Randomisation
|
230 participants
|
234 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomisation to once vs twice daily, week 48Population: All participants alive in follow-up with CD4%
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=331 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 48
|
0.9 percentage of total lymphocytes
Standard Deviation 6.1
|
1.3 percentage of total lymphocytes
Standard Deviation 5.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants alive in follow-up with CD4%
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=332 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=325 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 72
|
1.9 percentage of total lymphocytes
Standard Deviation 6.3
|
1.9 percentage of total lymphocytes
Standard Deviation 5.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomisation to once vs twice daily, week 96Population: All participants alive in follow-up with CD4%
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=306 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=304 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 96
|
1.6 percentage of lymphocytes
Standard Deviation 7.0
|
2.5 percentage of lymphocytes
Standard Deviation 6.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomisation to once vs twice daily, week 48Population: All participants aged \>5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
Estimated in those \>5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=193 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=170 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 48
|
3 cells per mm3
Standard Deviation 348
|
-3 cells per mm3
Standard Deviation 301
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants aged \>5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
All participants aged \>5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=190 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=165 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 72
|
-6 cells per mm3
Standard Deviation 350
|
27 cells per mm3
Standard Deviation 316
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomisation to once vs twice daily, week 96Population: All participants aged \>5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
All participants aged \>5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=171 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=149 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 96
|
-26 cells per mm3
Standard Deviation 445
|
60 cells per mm3
Standard Deviation 737
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)Number of participants who died, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: All-cause Mortality
|
1 participants
|
4 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: New WHO Stage 4 Event or Death
|
3 participants
|
7 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: New WHO Stage 3 or 4 Event or Death
|
9 participants
|
12 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Age-adjusted change in height-for-age Z-score over all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Height-for-age Z-score
|
0.28 age-adjusted z-score
Standard Deviation 0.36
|
0.32 age-adjusted z-score
Standard Deviation 0.45
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Weight-for-age Z-score
|
0.01 age-adjusted z-score
Standard Deviation 0.35
|
-0.00 age-adjusted z-score
Standard Deviation 0.37
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Body Mass Index-for-age Z-score
|
-0.29 age-adjusted z-score
Standard Deviation 0.49
|
-0.35 age-adjusted z-score
Standard Deviation 0.57
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
|
57 participants
|
54 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Number of participants with a new serious adverse event not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: New Serious Adverse Events Not Solely Related to HIV
|
30 participants
|
37 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 48 weeks after randomization to once- versus twice-dailyPopulation: All participants completing the questionnaire
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 48 weeks.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=330 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 48 Weeks
|
32 participants
|
29 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 96 weeks after randomization to once- versus twice-dailyPopulation: All participants completing the questionnaire
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 96 weeks.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=311 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=309 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 96 Weeks
|
26 participants
|
25 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Mean over median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=336 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=333 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
|
8 % of visits reporting missed pills
Standard Deviation 12
|
8 % of visits reporting missed pills
Standard Deviation 12
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new clinical and diagnostic positive malaria, to be analysed using time-to-event methods. Diagnostic positive by either microscopy (thick film) or rapid diagnostic test (RDT)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New Clinical and Diagnostic Positive Malaria
|
39 participants
|
77 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new severe pneumonia, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New Severe Pneumonia
|
7 participants
|
10 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New WHO Stage 3 or 4 Event or Death
|
8 participants
|
19 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new WHO stage 3 severe recurrent pneumonia or diarrhoea, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New WHO Stage 3 Severe Recurrent Pneumonia or Diarrhoea
|
1 participants
|
4 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New WHO Stage 4 Event or Death
|
4 participants
|
7 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants who died, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: All-cause Mortality
|
3 participants
|
2 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Weight-for-age Z-score
|
-0.01 age-adjusted z-score
Standard Deviation 0.37
|
-0.05 age-adjusted z-score
Standard Deviation 0.34
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Age-adjusted change in height-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Height-for-age Z-score
|
0.22 age-adjusted z-score
Standard Deviation 0.33
|
0.19 age-adjusted z-score
Standard Deviation 0.35
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Body Mass Index-for-age Z-score
|
-0.24 age-adjusted z-score
Standard Deviation 0.54
|
-0.28 age-adjusted z-score
Standard Deviation 0.45
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants alive in follow-up with CD4%
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=360 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=360 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Change From Baseline in CD4% to Week 72
|
1.7 percentage of total lymphocytes
Standard Deviation 5.5
|
1.1 percentage of total lymphocytes
Standard Deviation 5.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 72Population: All participants aged \>5 years at randomization to stop versus continue alive in follow-up with CD4 measured
Estimated in those \>5 years at randomization to stop vs continue, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=253 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=254 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Change From Baseline in Absolute CD4 to Week 72
|
7 cells per mm3
Standard Deviation 310
|
-2 cells per mm3
Standard Deviation 303
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Number of participants with a new serious adverse event not solely related to HIV, to be analysed using time-to-event methods
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: New Serious Adverse Events Not Solely Related to HIV
|
32 participants
|
48 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Mean over median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Outcome measures
| Measure |
Clinically Driven Monitoring (CDM)
n=376 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=382 Participants
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
|---|---|---|---|---|---|
|
Cotrimoxazole: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
|
9 % of visits reporting missed pills
Standard Deviation 13
|
8 % of visits reporting missed pills
Standard Deviation 13
|
—
|
—
|
—
|
Adverse Events
Clinically Driven Monitoring (CDM)
Serious events: 147 serious events
Other events: 190 other events
Deaths: 0 deaths
Laboratory Plus Clinical Monitoring (LCM)
Serious events: 117 serious events
Other events: 198 other events
Deaths: 0 deaths
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
Serious events: 87 serious events
Other events: 96 other events
Deaths: 0 deaths
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Serious events: 92 serious events
Other events: 124 other events
Deaths: 0 deaths
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Serious events: 95 serious events
Other events: 168 other events
Deaths: 0 deaths
Once-daily ABC+3TC
Serious events: 30 serious events
Other events: 33 other events
Deaths: 0 deaths
Twice-daily ABC+3TC
Serious events: 37 serious events
Other events: 26 other events
Deaths: 0 deaths
Continued Cotrimoxazole Prophylaxis
Serious events: 32 serious events
Other events: 37 other events
Deaths: 0 deaths
Stopped Cotrimoxazole Prophylaxis
Serious events: 48 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Clinically Driven Monitoring (CDM)
n=606 participants at risk
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 participants at risk
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
n=397 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 participants at risk
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI-\>ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 participants at risk
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI-\>ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Once-daily ABC+3TC
n=336 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
|
Twice-daily ABC+3TC
n=333 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Twice-daily ABC+3TC
|
Continued Cotrimoxazole Prophylaxis
n=376 participants at risk
Once-daily doses 5-\<15 kg: 200 mg of trimethoprim + 40 mg sulfamethoxazole 15-\<30 kg: 400 mg trimethoprim + 80 mg sulfamethoxazole \>=30 kg: 800 mg trimethoprim + 160 mg sulfamethoxazole
Continued cotrimoxazole prophylaxis
|
Stopped Cotrimoxazole Prophylaxis
n=382 participants at risk
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
|
|---|---|---|---|---|---|---|---|---|---|
|
Nervous system disorders
Coma
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/336 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Gastrointestinal disorders
Acute diarrhoea
|
1.7%
10/606 • Number of events 10 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.0%
6/600 • Number of events 6 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.0%
4/397 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.7%
7/404 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.2%
5/405 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.60%
2/336 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.80%
3/376 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/606 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Gastrointestinal disorders
Gasteroenteritis
|
0.50%
3/606 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.33%
2/600 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.74%
3/404 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.27%
1/376 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Gastrointestinal disorders
Vomiting
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Blood and lymphatic system disorders
Clinical Anaemia
|
2.8%
17/606 • Number of events 18 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.0%
12/600 • Number of events 12 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.5%
6/397 • Number of events 6 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.5%
10/404 • Number of events 11 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.2%
13/405 • Number of events 13 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.89%
3/336 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.0%
4/382 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchietasis
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
1.2%
7/606 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.2%
7/600 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.5%
6/397 • Number of events 6 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.74%
3/404 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.2%
5/405 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.60%
2/336 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.53%
2/376 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Bone fracture
|
0.83%
5/606 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.67%
4/600 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
2/397 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.99%
4/404 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.74%
3/405 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Psychiatric disorders
Manic psychosis
|
0.00%
0/606 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Trauma
|
0.66%
4/606 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.67%
4/600 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.76%
3/397 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
2/404 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.74%
3/405 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.60%
2/336 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.80%
3/376 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.26%
1/382 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Hypersensitivity reaction
|
3.6%
22/606 • Number of events 22 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.2%
19/600 • Number of events 19 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.8%
15/397 • Number of events 15 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.7%
15/404 • Number of events 15 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.7%
11/405 • Number of events 11 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.53%
2/376 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Infections and infestations
Measles
|
1.2%
7/606 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.67%
4/600 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.2%
5/404 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.5%
6/405 • Number of events 6 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/336 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.90%
3/333 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.27%
1/376 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.79%
3/382 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Infections and infestations
Malaria
|
12.9%
78/606 • Number of events 113 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
8.2%
49/600 • Number of events 65 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
12.1%
48/397 • Number of events 69 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
9.4%
38/404 • Number of events 54 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
10.1%
41/405 • Number of events 55 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
5.7%
19/336 • Number of events 27 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
7.8%
26/333 • Number of events 33 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
4.3%
16/376 • Number of events 19 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
8.9%
34/382 • Number of events 47 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Infections and infestations
Septicaemia/bacteremia (presumptive)
|
0.83%
5/606 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.83%
5/600 • Number of events 6 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.0%
4/397 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.99%
4/404 • Number of events 4 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.49%
2/405 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.60%
2/336 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.30%
1/333 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.53%
2/376 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.52%
2/382 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Investigations
Raised liver enzymes
|
0.00%
0/606 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Cardiac disorders
Hypertension
|
0.33%
2/606 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Gastrointestinal disorders
Chronic diarrhoea
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.33%
2/606 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
3/600 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
2/404 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.74%
3/405 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Hepatobiliary disorders
Acute hepatitis
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
3/600 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
2/397 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
2/404 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.27%
1/376 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm/asthma
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia/arthritis
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Nervous system disorders
Death, cause unknown
|
0.33%
2/606 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.50%
3/600 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.76%
3/397 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.49%
2/405 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Psychiatric disorders
Overdose
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Burns
|
0.00%
0/606 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.27%
1/376 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/405 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Blood and lymphatic system disorders
Pneumococcal septicaemia
|
0.33%
2/606 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Metabolism and nutrition disorders
Kwashiorkor
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/397 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Infections and infestations
Febrile convulsions
|
0.00%
0/606 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic sinusitis
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/600 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.25%
1/404 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/405 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
0.17%
1/606 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.17%
1/600 • Number of events 1 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/397 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/404 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.49%
2/405 • Number of events 2 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/336 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/333 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/376 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.00%
0/382 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
Other adverse events
| Measure |
Clinically Driven Monitoring (CDM)
n=606 participants at risk
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Laboratory Plus Clinical Monitoring (LCM)
n=600 participants at risk
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
|
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
n=397 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
n=404 participants at risk
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI-\>ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
n=405 participants at risk
ZDV \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI-\>ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
|
Once-daily ABC+3TC
n=336 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
|
Twice-daily ABC+3TC
n=333 participants at risk
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Twice-daily ABC+3TC
|
Continued Cotrimoxazole Prophylaxis
n=376 participants at risk
Once-daily doses 5-\<15 kg: 200 mg of trimethoprim + 40 mg sulfamethoxazole 15-\<30 kg: 400 mg trimethoprim + 80 mg sulfamethoxazole \>=30 kg: 800 mg trimethoprim + 160 mg sulfamethoxazole
Continued cotrimoxazole prophylaxis
|
Stopped Cotrimoxazole Prophylaxis
n=382 participants at risk
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
|
|---|---|---|---|---|---|---|---|---|---|
|
Infections and infestations
Anaemia with no clinical symptoms
|
4.8%
29/606 • Number of events 32 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
6.2%
37/600 • Number of events 41 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
5.0%
20/397 • Number of events 22 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
5.4%
22/404 • Number of events 26 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
5.9%
24/405 • Number of events 25 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
0.89%
3/336 • Number of events 3 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.5%
5/333 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.3%
5/376 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.3%
5/382 • Number of events 5 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Investigations
Neutropenia with no clinical symptoms
|
24.9%
151/606 • Number of events 211 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
26.7%
160/600 • Number of events 206 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
17.4%
69/397 • Number of events 92 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
26.0%
105/404 • Number of events 138 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
33.8%
137/405 • Number of events 187 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
6.5%
22/336 • Number of events 27 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
4.5%
15/333 • Number of events 16 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
6.9%
26/376 • Number of events 28 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
4.7%
18/382 • Number of events 23 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
|
Investigations
Thrombocytopenia with no clinical symptoms
|
5.3%
32/606 • Number of events 44 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.5%
21/600 • Number of events 29 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
4.8%
19/397 • Number of events 24 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
3.0%
12/404 • Number of events 14 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
5.4%
22/405 • Number of events 35 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.7%
9/336 • Number of events 15 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.1%
7/333 • Number of events 7 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
2.7%
10/376 • Number of events 14 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
1.6%
6/382 • Number of events 12 • LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
|
Additional Information
Professor Ann Sarah Walker
Medical Research Council
Phone: +44 20 7670 4726
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place