Trial Outcomes & Findings for Immediate Versus Deferred Start of Anti-HIV Therapy in HIV-Infected Adults Being Treated for Tuberculosis (NCT NCT00108862)
NCT ID: NCT00108862
Last Updated: 2018-10-11
Results Overview
As this was a study of the strategy of providing antiretroviral therapy (ART) during the initial treatment of TB versus deferring ART until TB was treated for 8-12 weeks, all eligible participants randomized were followed for 48 weeks, whether they started ART as scheduled, whether they started ART at all, or even if the participant did not have TB and discontinued TB treatment. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
809 participants
Primary outcome timeframe
Through week 48
Results posted on
2018-10-11
Participant Flow
Study participants were recruited at 26 sites from 13 countries: 4 each from U.S. and South Africa; 3 from Brazil; 2 each from Peru, Botswana, Kenya, Malawi, and India; and 1 each from Haiti, Uganda, Zambia, Zimbabwe, and Thailand, between September 2006 and August 2009.
HIV-infected persons at least 13 years of age, naive to antiretroviral therapy, who had received 1-14 cumulative days of a rifamycin-based TB regimen within 28 days prior to study entry, and had a CD4 count \<250 cells/mm3. Randomization was stratified by screening CD4 (\<50 vs =\>50). Three participants were deemed ineligible and taken off study.
Participant milestones
| Measure |
Immediate ART
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Overall Study
STARTED
|
405
|
401
|
|
Overall Study
COMPLETED
|
337
|
339
|
|
Overall Study
NOT COMPLETED
|
68
|
62
|
Reasons for withdrawal
| Measure |
Immediate ART
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Overall Study
Death
|
31
|
37
|
|
Overall Study
Withdrawal by Subject
|
10
|
6
|
|
Overall Study
Lost to Follow-up
|
27
|
19
|
Baseline Characteristics
Immediate Versus Deferred Start of Anti-HIV Therapy in HIV-Infected Adults Being Treated for Tuberculosis
Baseline characteristics by cohort
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Total
n=806 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
403 Participants
n=5 Participants
|
398 Participants
n=7 Participants
|
801 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
34 years
n=5 Participants
|
34 years
n=7 Participants
|
34 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=5 Participants
|
166 Participants
n=7 Participants
|
305 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
266 Participants
n=5 Participants
|
235 Participants
n=7 Participants
|
501 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
109 participants
n=5 Participants
|
112 participants
n=7 Participants
|
221 participants
n=5 Participants
|
|
Region of Enrollment
Malawi
|
69 participants
n=5 Participants
|
68 participants
n=7 Participants
|
137 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
57 participants
n=5 Participants
|
56 participants
n=7 Participants
|
113 participants
n=5 Participants
|
|
Region of Enrollment
Kenya
|
36 participants
n=5 Participants
|
36 participants
n=7 Participants
|
72 participants
n=5 Participants
|
|
Region of Enrollment
Peru
|
23 participants
n=5 Participants
|
25 participants
n=7 Participants
|
48 participants
n=5 Participants
|
|
Region of Enrollment
India
|
26 participants
n=5 Participants
|
21 participants
n=7 Participants
|
47 participants
n=5 Participants
|
|
Region of Enrollment
Zambia
|
17 participants
n=5 Participants
|
17 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Region of Enrollment
Zimbabwe
|
16 participants
n=5 Participants
|
17 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Region of Enrollment
Uganda
|
15 participants
n=5 Participants
|
14 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
Botswana
|
13 participants
n=5 Participants
|
15 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Haiti
|
12 participants
n=5 Participants
|
8 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
10 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
TB Diagnosis Level at Entry
Confirmed TB
|
193 participants
n=5 Participants
|
181 participants
n=7 Participants
|
374 participants
n=5 Participants
|
|
TB Diagnosis Level at Entry
Probable TB
|
208 participants
n=5 Participants
|
218 participants
n=7 Participants
|
426 participants
n=5 Participants
|
|
TB Diagnosis Level at Entry
Not TB
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Drug-Resistant TB Status at Entry
Rifampin (RIF) Resistant TB
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Drug-Resistant TB Status at Entry
Isoniazid (INH) Resistant TB
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Drug-Resistant TB Status at Entry
RIF and INH Resistant TB (Multi-Drug Resistant TB)
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Drug-Resistant TB Status at Entry
RIF and INH Sensitive TB
|
400 participants
n=5 Participants
|
392 participants
n=7 Participants
|
792 participants
n=5 Participants
|
|
Time to ART Start from Start of TB Medications
|
10 days
n=5 Participants
|
70 days
n=7 Participants
|
14 days
n=5 Participants
|
PRIMARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
As this was a study of the strategy of providing antiretroviral therapy (ART) during the initial treatment of TB versus deferring ART until TB was treated for 8-12 weeks, all eligible participants randomized were followed for 48 weeks, whether they started ART as scheduled, whether they started ART at all, or even if the participant did not have TB and discontinued TB treatment. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants Who Survived Without AIDS Progression.
|
13 percent of participants
Interval 10.0 to 16.0
|
16 percent of participants
Interval 12.0 to 20.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in this analysis. The percent of participants whose highest reported grade of adverse events and laboratory abnormalities was Grade 3 or 4 was calculated with an associated standard error, where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening/disabling, and Grade 5=death.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality
|
44 percent of participants
Interval 39.0 to 49.0
|
47 percent of participants
Interval 42.0 to 52.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in this analysis. Weeks from randomization to first new AIDS-defining illness or death was analyzed using a stratified Cox proportional hazards regression model. The stratification was by screening CD4 cell count: \<50 cells/mm3 versus =\>50 cells/mm3.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Time to First New AIDS-defining Illness or Death.
5th percentile
|
4 weeks
Interval 3.0 to 8.0
|
7 weeks
Interval 4.0 to 10.0
|
|
Time to First New AIDS-defining Illness or Death.
10th percentile
|
13 weeks
Interval 8.0 to 49.0
|
12 weeks
Interval 9.0 to 19.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
This analysis was based on 374 participants with culture-confirmed TB at entry. The percent with culture-confirmed TB surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=193 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=181 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression.
|
12 percent of participants
Interval 7.0 to 17.0
|
17 percent of participants
Interval 12.0 to 23.0
|
SECONDARY outcome
Timeframe: Through week 48All eligible participants were included in this analysis. The percent of participants who interrupted at least one TB medication for more than one day due to toxicity or discontinued at least one TB medication due to toxicity was calculated with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity.
|
9 percent of participants
Interval 6.0 to 12.0
|
10 percent of participants
Interval 7.0 to 13.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Participants with confirmed or probable TB at study entry were included in this analysis. Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
TB treatment outcome was assessed in the 800 eligible participants who had confirmed or probable TB at study entry. The sites determined if the TB was resolved. If TB was not resolved, TB treatment outcome status was determined based on whether TB treatment was ongoing at the last study visit; if the participant died while TB treatment was ongoing; or if the participant was lost to follow-up, withdrew consent, or other reason for lacking TB resolution status. Percents were calculated with associated standard errors.
Outcome measures
| Measure |
Immediate ART
n=401 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=399 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.
TB Resolved
|
79 percent of participants
Interval 75.0 to 83.0
|
82 percent of participants
Interval 78.0 to 85.0
|
|
Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.
TB Treatment Ongoing
|
6 percent of participants
Interval 4.0 to 9.0
|
5 percent of participants
Interval 3.0 to 8.0
|
|
Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.
Death
|
6 percent of participants
Interval 4.0 to 9.0
|
7 percent of participants
Interval 5.0 to 10.0
|
|
Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.
Lost-to-Follow-up/Withdrew Consent/Other
|
8 percent of participants
Interval 5.0 to 11.0
|
6 percent of participants
Interval 4.0 to 9.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in the analysis. Participants who were lost-to-follow-up (LFU) prior to week 48 or who were alive with a CD4 cell count increase of less than 100 cells/mm\^3 were grouped separately those who died or whose CD4 cell count increased by at least 100 cells/mm\^3. Participants missing CD4 cell counts at week 48 were coded as LFU in this analysis. The percents were calculated with associated standard errors.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48.
CD4 increase of at least 100 cells/mm^3
|
60 percent of participants
Interval 55.0 to 65.0
|
60 percent of participants
Interval 55.0 to 65.0
|
|
Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48.
LFU, or alive with CD4 increase < 100 cells/mm^3
|
32 percent of participants
Interval 28.0 to 37.0
|
31 percent of participants
Interval 26.0 to 35.0
|
|
Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48.
Dead
|
8 percent of participants
Interval 5.0 to 11.0
|
9 percent of participants
Interval 7.0 to 13.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in this analysis. The percent of participants with Mycobacteria tuberculosis (MTB)-associated immune reconstitution inflammatory syndrome (IRIS) was calculated with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants With MTB IRIS.
|
11 percent of participants
Interval 8.0 to 14.0
|
5 percent of participants
Interval 3.0 to 7.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in this analysis. The percent of participants with HIV-associated immune reconstitution inflammatory syndrome (IRIS) was calculated with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants With HIV IRIS.
|
3 percent of participants
Interval 2.0 to 5.0
|
3 percent of participants
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
All eligible participants were included in the analysis. Participants who were lost-to-follow-up (LFU) prior to week 48 or who were alive with a HIV viral load at least 400 copies/mL were grouped separately those those who died or who had HIV viral loads below 400 copies/mL. Participants missing HIV viral loads at week 48 were coded as LFU in this analysis. Percents were calculated with associated standard errors.
Outcome measures
| Measure |
Immediate ART
n=405 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.
HIV viral load < 400 copies/mL
|
72 percent of participants
Interval 68.0 to 77.0
|
75 percent of participants
Interval 71.0 to 79.0
|
|
Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.
LFU, or alive with HIV viral load at least 400
|
20 percent of participants
Interval 16.0 to 24.0
|
16 percent of participants
Interval 12.0 to 20.0
|
|
Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.
Dead
|
8 percent of participants
Interval 5.0 to 11.0
|
9 percent of participants
Interval 7.0 to 13.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
Participants were included as described in the Outcome Measure Description for the Primary Outcome, except that only those in the \<50 CD4 stratum were analyzed. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=144 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=141 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.
|
16 percent of participants
Interval 10.0 to 21.0
|
27 percent of participants
Interval 19.0 to 39.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Through week 48Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
Participants were included as described in the Outcome Measure Description for the Primary Outcome, except that only those in the =\>50 CD4 stratum were analyzed. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
Outcome measures
| Measure |
Immediate ART
n=261 Participants
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=260 Participants
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.
|
11 percent of participants
Interval 8.0 to 15.0
|
10 percent of participants
Interval 7.0 to 14.0
|
Adverse Events
Immediate ART
Serious events: 55 serious events
Other events: 391 other events
Deaths: 0 deaths
Deferred ART
Serious events: 44 serious events
Other events: 389 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Immediate ART
n=405 participants at risk
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 participants at risk
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.5%
6/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.25%
1/405 • Through week 48
|
0.75%
3/401 • Through week 48
|
|
Cardiac disorders
Cardiac failure congestive
|
0.25%
1/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Gastrointestinal disorders
Ascites
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Gastrointestinal disorders
Diarrhoea
|
0.49%
2/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Gastrointestinal disorders
Vomiting
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
General disorders
Death
|
0.49%
2/405 • Through week 48
|
1.5%
6/401 • Through week 48
|
|
General disorders
Pyrexia
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Hepatobiliary disorders
Hepatitis
|
0.25%
1/405 • Through week 48
|
0.50%
2/401 • Through week 48
|
|
Hepatobiliary disorders
Hepatitis alcoholic
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Hepatobiliary disorders
Hepatotoxicity
|
1.2%
5/405 • Through week 48
|
1.00%
4/401 • Through week 48
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.25%
1/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Infections and infestations
Bacterial sepsis
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/405 • Through week 48
|
0.50%
2/401 • Through week 48
|
|
Infections and infestations
Meningitis bacterial
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Infections and infestations
Meningitis cryptococcal
|
0.00%
0/405 • Through week 48
|
0.75%
3/401 • Through week 48
|
|
Infections and infestations
Meningitis tuberculous
|
0.49%
2/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Infections and infestations
Mycobacterium avium complex infection
|
0.49%
2/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Infections and infestations
Pneumonia bacterial
|
0.25%
1/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Infections and infestations
Pulmonary tuberculosis
|
1.7%
7/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Infections and infestations
Sepsis
|
0.00%
0/405 • Through week 48
|
0.75%
3/401 • Through week 48
|
|
Infections and infestations
Tuberculoma of central nervous system
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Infections and infestations
Tuberculosis
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Infections and infestations
Viral myocarditis
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.25%
1/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Investigations
Aspartate aminotransferase increased
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Investigations
Blood creatinine increased
|
0.25%
1/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/405 • Through week 48
|
1.00%
4/401 • Through week 48
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.49%
2/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.25%
1/405 • Through week 48
|
0.75%
3/401 • Through week 48
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Nervous system disorders
Central nervous system mass
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Nervous system disorders
Coma hepatic
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Nervous system disorders
Encephalitis
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Nervous system disorders
Hemiplegia
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Nervous system disorders
Intracranial pressure increased
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Psychiatric disorders
Confusional state
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Renal and urinary disorders
Renal failure
|
0.74%
3/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Renal and urinary disorders
Renal failure acute
|
0.74%
3/405 • Through week 48
|
0.50%
2/401 • Through week 48
|
|
Renal and urinary disorders
Renal impairment
|
0.49%
2/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.25%
1/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.49%
2/405 • Through week 48
|
0.00%
0/401 • Through week 48
|
|
Vascular disorders
Shock
|
0.00%
0/405 • Through week 48
|
0.25%
1/401 • Through week 48
|
Other adverse events
| Measure |
Immediate ART
n=405 participants at risk
These participants initiated HIV antiretroviral therapy (ART) within 72 hours of randomization, which took place at most 2 weeks after initiating rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were efavirenz (EFV) 600 mg (provided to non-U.S. sites only; 1 tablet orally) and emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered nevirapine (NVP) 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals (ARVs) that were compatible with TB therapy could be used at the discretion of the site investigator.
|
Deferred ART
n=401 participants at risk
These participants deferred ART until 8 to 12 weeks after initiation of their RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided drugs were EFV 600 mg (provided to non-U.S. sites only; 1 tablet orally) and FTC 200 mg/TDF 300 mg (1 fixed-dose combination tablet orally) once daily. FTC 200 mg (1 capsule) and TDF 300 mg (1 tablet) could be substituted for the fixed-dose combination tablet and was provided by the study. Participants who could not tolerate EFV could be offered NVP 200 mg daily for 14 days, then 200 mg twice daily. Substitutions with other locally-available U.S. FDA-approved or tentatively approved ARVs that were compatible with TB therapy could be used at the discretion of the site investigator.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
9.1%
37/405 • Through week 48
|
4.7%
19/401 • Through week 48
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
27/405 • Through week 48
|
5.2%
21/401 • Through week 48
|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
23/405 • Through week 48
|
8.2%
33/401 • Through week 48
|
|
Gastrointestinal disorders
Leukoplakia oral
|
4.9%
20/405 • Through week 48
|
7.5%
30/401 • Through week 48
|
|
Gastrointestinal disorders
Nausea
|
5.2%
21/405 • Through week 48
|
4.5%
18/401 • Through week 48
|
|
Gastrointestinal disorders
Vomiting
|
10.4%
42/405 • Through week 48
|
9.7%
39/401 • Through week 48
|
|
General disorders
Chest pain
|
6.4%
26/405 • Through week 48
|
5.0%
20/401 • Through week 48
|
|
General disorders
Pyrexia
|
18.5%
75/405 • Through week 48
|
15.7%
63/401 • Through week 48
|
|
Infections and infestations
Herpes zoster
|
4.7%
19/405 • Through week 48
|
5.5%
22/401 • Through week 48
|
|
Infections and infestations
Oral candidiasis
|
11.6%
47/405 • Through week 48
|
19.5%
78/401 • Through week 48
|
|
Infections and infestations
Pneumonia bacterial
|
7.2%
29/405 • Through week 48
|
8.5%
34/401 • Through week 48
|
|
Investigations
Alanine aminotransferase increased
|
19.5%
79/405 • Through week 48
|
20.4%
82/401 • Through week 48
|
|
Investigations
Aspartate aminotransferase increased
|
32.6%
132/405 • Through week 48
|
37.9%
152/401 • Through week 48
|
|
Investigations
Blood albumin
|
4.4%
18/405 • Through week 48
|
5.2%
21/401 • Through week 48
|
|
Investigations
Blood albumin abnormal
|
75.8%
307/405 • Through week 48
|
80.5%
323/401 • Through week 48
|
|
Investigations
Blood alkaline phosphatase increased
|
32.8%
133/405 • Through week 48
|
34.4%
138/401 • Through week 48
|
|
Investigations
Blood bicarbonate abnormal
|
19.3%
78/405 • Through week 48
|
22.2%
89/401 • Through week 48
|
|
Investigations
Blood bilirubin increased
|
6.4%
26/405 • Through week 48
|
6.7%
27/401 • Through week 48
|
|
Investigations
Blood creatinine increased
|
7.2%
29/405 • Through week 48
|
7.0%
28/401 • Through week 48
|
|
Investigations
Blood phosphorus decreased
|
17.5%
71/405 • Through week 48
|
14.0%
56/401 • Through week 48
|
|
Investigations
Blood potassium decreased
|
9.4%
38/405 • Through week 48
|
8.2%
33/401 • Through week 48
|
|
Investigations
Blood sodium decreased
|
52.3%
212/405 • Through week 48
|
56.6%
227/401 • Through week 48
|
|
Investigations
Haemoglobin decreased
|
52.1%
211/405 • Through week 48
|
53.6%
215/401 • Through week 48
|
|
Investigations
Neutrophil count decreased
|
21.2%
86/405 • Through week 48
|
25.4%
102/401 • Through week 48
|
|
Investigations
Platelet count decreased
|
4.7%
19/405 • Through week 48
|
8.5%
34/401 • Through week 48
|
|
Investigations
Weight decreased
|
5.2%
21/405 • Through week 48
|
4.0%
16/401 • Through week 48
|
|
Investigations
White blood cell count decreased
|
15.8%
64/405 • Through week 48
|
18.7%
75/401 • Through week 48
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
27/405 • Through week 48
|
5.5%
22/401 • Through week 48
|
|
Nervous system disorders
Dizziness
|
8.1%
33/405 • Through week 48
|
7.7%
31/401 • Through week 48
|
|
Nervous system disorders
Headache
|
10.1%
41/405 • Through week 48
|
13.2%
53/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.6%
47/405 • Through week 48
|
11.0%
44/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.1%
33/405 • Through week 48
|
6.2%
25/401 • Through week 48
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal plaque
|
5.2%
21/405 • Through week 48
|
9.7%
39/401 • Through week 48
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.2%
9/405 • Through week 48
|
6.0%
24/401 • Through week 48
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.6%
35/405 • Through week 48
|
12.2%
49/401 • Through week 48
|
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 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