Trial Outcomes & Findings for Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults (NCT NCT00608569)

Last Updated: 2018-10-12

Results Overview

Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) \<1 log10 copies/mL below the baseline level and \>400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) \>400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤50 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 48 was reported.

Recruitment status

COMPLETED

Study phase

Target enrollment

529 participants

Primary outcome timeframe

At or prior to Week 48

Results posted on

2018-10-12

Participant Flow

Participants were recruited across 9 study sites (2 in Peru, one each in South Africa, Haiti, Uganda, Botswana, Zimbabwe, Brazil and Zambia) in the AIDS Clinical Trials Group system between April 2009 and September 2011.

Five hundred twenty nine subjects including participants and partners entered the study. Among the 529 subjects, 259 were participants, which included two participants with eligibility violations. Only the 257 eligible participants were included in the analyses. All participants started TDF/FTC +LPV/rtv and stratified by screening HIV-1 RNA only.

Participant milestones

Participant milestones
Measure	mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Study STARTED	129	128
Overall Study COMPLETED	119	119
Overall Study NOT COMPLETED	10	9

Reasons for withdrawal

Reasons for withdrawal
Measure	mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Study Death	4	3
Overall Study Lost to Follow-up	4	5
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	0
Overall Study Unable to adhere with study requirements	0	1

Baseline Characteristics

Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.	Total n=257 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	127 Participants n=5 Participants	123 Participants n=7 Participants	250 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	39.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	39.4 years STANDARD_DEVIATION 10.6 • n=7 Participants	39.4 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	65 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	63 Participants n=7 Participants	130 Participants n=5 Participants
Race/Ethnicity, Customized Black Non-Hispanic	101 participants n=5 Participants	103 participants n=7 Participants	204 participants n=5 Participants
Race/Ethnicity, Customized Hispanic (regardless of race)	27 participants n=5 Participants	25 participants n=7 Participants	52 participants n=5 Participants
Race/Ethnicity, Customized More than one race	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Haiti	37 participants n=5 Participants	36 participants n=7 Participants	73 participants n=5 Participants
Region of Enrollment Zambia	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Botswana	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Peru	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment Uganda	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment South Africa	15 participants n=5 Participants	17 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Zimbabwe	17 participants n=5 Participants	16 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Brazil	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
CD4 Counts	164 cells/mm3 n=5 Participants	201 cells/mm3 n=7 Participants	179 cells/mm3 n=5 Participants
CD4 Count Category 0-50 cells/mm3	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
CD4 Count Category 51-100 cells/mm3	20 participants n=5 Participants	19 participants n=7 Participants	39 participants n=5 Participants
CD4 Count Category 101-200 cells/mm3	40 participants n=5 Participants	31 participants n=7 Participants	71 participants n=5 Participants
CD4 Count Category 201-350 cells/mm3	35 participants n=5 Participants	47 participants n=7 Participants	82 participants n=5 Participants
CD4 Count Category 351-500 cells/mm3	9 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants
CD4 Count Category >500 cells/mm3	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Log10 HIV-1 RNA Viral Load	4.2 log10 copies/mL n=5 Participants	4.3 log10 copies/mL n=7 Participants	4.3 log10 copies/mL n=5 Participants
HIV-1 RNA Viral Load Category <=400 copies/mL	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
HIV-1 RNA Viral Load Category 401-999 copies/mL	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
HIV-1 RNA Viral Load Category 1000-9999 copies/mL	42 participants n=5 Participants	38 participants n=7 Participants	80 participants n=5 Participants
HIV-1 RNA Viral Load Category 10000-99999 copies/mL	54 participants n=5 Participants	55 participants n=7 Participants	109 participants n=5 Participants
HIV-1 RNA Viral Load Category 100000-499999 copies/mL	17 participants n=5 Participants	24 participants n=7 Participants	41 participants n=5 Participants
HIV-1 RNA Viral Load Category >=500000 copies/mL	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: At or prior to Week 48

Population: Two hundred fifty seven eligible participants were included in the analysis. Intent to treat analysis was performed.

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Confirmed Virologic Failure at or Prior to Week 48 No Failure	95 participants	105 participants
Confirmed Virologic Failure at or Prior to Week 48 Experienced Failure	34 participants	23 participants

SECONDARY outcome

Timeframe: At or prior to Week 24

Population: Two hundred fifty seven eligible participants were included in the analysis. Intent to treat analysis was performed.

Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) \<1 log10 copies/mL below the baseline level and \>400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) \>400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤30 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 24 was reported.

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Confirmed Virologic Failure at or Prior to Week 24 No Failure	105 participants	111 participants
Confirmed Virologic Failure at or Prior to Week 24 Experienced Failure	24 participants	17 participants

SECONDARY outcome

Timeframe: At Weeks 4, 12, 24, 36, and 48

CD4 cell count (median, inter-quartile range)

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
CD4 Count at Follow-up Visits Week 4	212 cells/mm3 Interval 129.0 to 309.0	219 cells/mm3 Interval 158.0 to 289.0
CD4 Count at Follow-up Visits Week 12	225 cells/mm3 Interval 168.0 to 359.0	235 cells/mm3 Interval 174.0 to 337.0
CD4 Count at Follow-up Visits Week 24	268 cells/mm3 Interval 177.0 to 382.0	266 cells/mm3 Interval 181.0 to 395.0
CD4 Count at Follow-up Visits Week 36	281 cells/mm3 Interval 189.0 to 395.0	294 cells/mm3 Interval 214.0 to 418.0
CD4 Count at Follow-up Visits Week 48	301 cells/mm3 Interval 198.0 to 432.0	347 cells/mm3 Interval 234.0 to 466.0

SECONDARY outcome

Timeframe: At week 4, 12, 24, 36, and 48

CD8 cell count (median, inter-quartile range)

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
CD8 Count at Follow-up Visits Week 4	776 cells/mm3 Interval 557.0 to 1048.0	859 cells/mm3 Interval 557.0 to 1141.0
CD8 Count at Follow-up Visits Week 12	895 cells/mm3 Interval 625.0 to 1155.0	916 cells/mm3 Interval 635.0 to 1290.0
CD8 Count at Follow-up Visits Week 24	816 cells/mm3 Interval 586.0 to 1071.0	818 cells/mm3 Interval 547.0 to 1126.0
CD8 Count at Follow-up Visits Week 36	787 cells/mm3 Interval 539.0 to 1034.0	833 cells/mm3 Interval 598.0 to 1131.0
CD8 Count at Follow-up Visits Week 48	815 cells/mm3 Interval 566.0 to 1037.0	823 cells/mm3 Interval 573.0 to 1125.0

SECONDARY outcome

Timeframe: 52 weeks since randomization

Population: Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.

5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Time to First Grade 3 or 4 Lab Event 5th percentile	24 weeks Interval 1.3 to Not estimable as the upper limit for survival function at all weeks is above 95%	NA weeks Interval 12.0 to Not estimable as the estimates for survival function at all weeks is above 95%
Time to First Grade 3 or 4 Lab Event 10th percentile	NA weeks Interval 12.0 to Not estimable as the estimates for survival function at all weeks is above 90%	NA weeks Interval 36.9 to Not estimable as the estimates for survival function at all weeks is above 90%

SECONDARY outcome

Timeframe: 52 weeks since randomization

Population: Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.

5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Time to First Grade 3 or 4 Sign or Symptom 5th percentile	13.7 weeks Interval 0.0 to 48.0	26.7 weeks Interval 0.3 to 48.9
Time to First Grade 3 or 4 Sign or Symptom 10th percentile	NA weeks Interval 12.0 to Not estimable as the estimates for survival function at all weeks is above 90%	48.9 weeks Interval 12.0 to Not estimable as the upper limit for survival function at all weeks is above 90%

SECONDARY outcome

Timeframe: 52 weeks since randomization

Population: Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.

5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab or sign/ symptom event

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Time to First Grade 3 or 4 Lab or Sign/Symptom Event 5th percentile	6.4 weeks Interval 0.0 to 13.7	24 weeks Interval 0.3 to 32.1
Time to First Grade 3 or 4 Lab or Sign/Symptom Event 10th percentile	24 weeks Interval 4.4 to 48.0	32.6 weeks Interval 12.0 to Not estimable as the upper limit for survival function at all weeks is above 90%

SECONDARY outcome

Timeframe: At weeks 4, 8, 12, 24, 36, 48 and 52

Population: Only the 257 eligible participants were included in the analysis. Self-reported adherence was collected face-to-face or by self-report on the Adherence/Quality of Life/Psychosocial Interview form. Only adherence to LPV/rtv was collected.

Number of participants with self-reported 100% adherence over the week prior to study visit

Outcome measures

Outcome measures
Measure	mDOT Arm n=129 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 Participants Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Adherence to Second Line HAART Regimen Week 4	105 participants	117 participants
Adherence to Second Line HAART Regimen Week 8	108 participants	115 participants
Adherence to Second Line HAART Regimen Week 12	114 participants	116 participants
Adherence to Second Line HAART Regimen Week 24	107 participants	116 participants
Adherence to Second Line HAART Regimen Week 48	103 participants	109 participants
Adherence to Second Line HAART Regimen Week 52	104 participants	109 participants

Adverse Events

mDOT Arm

Serious events: 6 serious events

Other events: 94 other events

Deaths: 0 deaths

Non-mDOT Arm

Serious events: 7 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	mDOT Arm n=129 participants at risk Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 participants at risk Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Pancreatitis	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
General disorders Death	1.6% 2/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Infections and infestations Bronchopneumonia	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Metabolism and nutrition disorders Dehydration	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Metabolism and nutrition disorders Diabetes mellitus	0.78% 1/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.78% 1/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Pregnancy, puerperium and perinatal conditions Ruptured ectopic pregnancy	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Psychiatric disorders Delirium	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Renal and urinary disorders Renal failure	1.6% 2/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.78% 1/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).

Other adverse events

Additional Information

ACTG ClinicalTrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights".
Publication restrictions are in place

Restriction type: OTHER

Measure	mDOT Arm n=129 participants at risk Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.	Non-mDOT Arm n=128 participants at risk Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Gastrointestinal disorders Abdominal pain	3.1% 4/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	7.0% 9/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Diarrhoea	12.4% 16/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	14.1% 18/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Vomiting	4.7% 6/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	7.0% 9/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
General disorders Chest pain	5.4% 7/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	3.9% 5/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
General disorders Pyrexia	8.5% 11/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	11.7% 15/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Infections and infestations Urinary tract infection	3.1% 4/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	7.8% 10/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Aspartate aminotransferase increased	10.1% 13/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	10.9% 14/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood alkaline phosphatase increased	11.6% 15/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	6.2% 8/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood bicarbonate abnormal	7.0% 9/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	6.2% 8/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood cholesterol	0.00% 0/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	5.5% 7/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood glucose increased	10.9% 14/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	7.0% 9/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood sodium decreased	21.7% 28/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	14.8% 19/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood sodium increased	6.2% 8/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	2.3% 3/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Haemoglobin decreased	6.2% 8/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	10.9% 14/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Neutrophil count decreased	31.0% 40/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	37.5% 48/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Weight decreased	6.2% 8/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	6.2% 8/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations White blood cell count decreased	18.6% 24/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	16.4% 21/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Nervous system disorders Headache	5.4% 7/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	7.0% 9/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Respiratory, thoracic and mediastinal disorders Cough	10.1% 13/129 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	11.7% 15/128 • 52 weeks since randomization Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).