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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01AI068636 | U.S. NIH Grant/Contract | View source | |
| ACTG A5221 | Other Identifier | AIDS Clinical Trials Group |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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The purpose of this study is to determine the best time to begin anti-HIV treatment in individuals who have HIV and tuberculosis (TB).
Study hypothesis: Immediate antiretroviral therapy (ART), initiated after approximately 2 weeks of TB treatment, will reduce the frequency of other AIDS-defining illnesses and death in HIV-infected participants being treated for TB by at least 40% at week 48 when compared to deferred ART, initiated at after 8-12 weeks of TB treatment.
Tuberculosis (TB) is the most important co-infection in the HIV epidemic; the bi-directional relationship between the two diseases is well established. HIV increases the risk for TB acquisition, reactivation, and reinfection, and reduces survival compared to patients with TB alone. In individuals with HIV, TB infection results in reduced survival, increased risk for opportunistic infections, and elevations in HIV replication. Improving the outcome of HIV-infected individuals who develop TB is of high importance. Initiating antiretroviral therapy (ART) shortly after initiating TB treatment may improve outcomes in individuals co-infected with HIV and TB. However, data to support this suggestion were limited before this study began. This study will determine the most appropriate time to initiate ART in HIV-infected individuals who recently initiated treatment for TB.
This study lasted 48 weeks and comprised two steps. At study entry, participants underwent clinical assessment, drug adherence training, and blood collection. In Step 1, participants were randomly assigned to one of two arms. Participants in Arm A initiated ART after approximately 2 weeks of TB treatment. Participants in Arm B deferred ART until after 8 to 12 weeks of TB treatment. In Step 2, Arm B participants initiated ART; Arm A participants did not enter Step 2. ART consisted of efavirenz (EFV) and emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC and TDF could be given as individual agents. Drug substitutions could be made for participants who could not tolerate the specified regimen. Blood collection and clinical assessments occurred at weeks 4, 8, 12, 16, 24, 32, 40, and 48.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immediate ART | Experimental | The intervention is the strategy of initiating antiretroviral therapy (ART) after approximately 2 weeks of tuberculosis (TB) treatment. |
|
| Deferred ART | Active Comparator | The intervention is the strategy of initiating ART after 8 to 12 weeks of TB treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Strategy: Immediate ART | Other | The intervention is the strategy of initiating antiretroviral therapy (ART) after approximately 2 weeks of rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided ART is efavirenz (EFV) 600 mg (1 tablet orally), emtricitabine (FTC) 200 mg (1 capsule orally), and tenofovir disoproxil fumarate (TDF) 300 mg (1 tablet orally) daily. Substitutions with other locally available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals that are compatible with TB treatment may be used at the discretion of the site investigator. The TB treatment will be supplied and monitored by the host country TB control program. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants Who Survived Without AIDS Progression. | 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. | Through week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diane Havlir, MD | San Francisco General Hospital and University of California, San Francisco | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California (1201) | Los Angeles | California | 90033-1079 | United States | ||
| University of California, San Diego, AVRC CRS (701) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25582793 | Derived | Crump JA, Wu X, Kendall MA, Ive PD, Kumwenda JJ, Grinsztejn B, Jentsch U, Swindells S. Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study. BMC Infect Dis. 2015 Jan 13;15:12. doi: 10.1186/s12879-014-0735-5. | |
| 22010914 | Derived | Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Strategy: Deferred ART | Other | The intervention is the strategy of initiating ART either after 8-12 weeks of RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided ART is EFV 600 mg (1 tablet orally), FTC 200 mg (1 capsule orally), and TDF 300 mg (1 tablet orally) daily. Initiation outside of these windows, on a case by case basis, is permitted at the discretion of the site investigator. Substitutions with other locally available U.S. FDA-approved or tentatively approved antiretrovirals that are compatible with TB treatment may be used at the discretion of the site investigator. The TB treatment will be supplied and monitored by the host country TB control program. |
|
|
| Through week 48 |
| Time to First New AIDS-defining Illness or Death. | 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. | Through week 48 |
| Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. | 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. | Through week 48 |
| Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. | All 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. | Through week 48 |
| 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 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. | Through week 48 |
| Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. | 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. | Through week 48 |
| Percent of Participants With MTB IRIS. | 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. | Through week 48 |
| Percent of Participants With HIV IRIS. | 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. | Through week 48 |
| Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | 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. | Through week 48 |
| Through week 48 |
| Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 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. | Through week 48 |
| San Diego |
| California |
| 92103 |
| United States |
| University of California, San Francisco AIDS CRS (801) | San Francisco | California | 94110 | United States |
| NY Univ. HIV/AIDS CRS (401) | New York | New York | 10016 | United States |
| Gaborone Prevention/Treatment Trials CRS (12701) | Gaborone | Botswana |
| Molepolole Prevention/Treatment Trials CRS (12702) | Molepolole | Botswana |
| Hospital Nossa Senhora da Conceicao CRS (12201) | Porto Alegre | Rio Grande do Sul | 9043010 | Brazil |
| Instituto de Pesquisa Clinica Evandro Chagas (12101) | Rio de Janeiro | 21045 | Brazil |
| Projecto Praca Onze/Hesfa CRS (30333) | Rio de Janeiro | Brazil |
| Les Centres GHESKIO CRS (30022) | Bicentenaire | Port-au-Prince | HT-6110 | Haiti |
| National AIDS Research Institute Pune CRS (11601) | Pune | Maharashtra | 411026 | India |
| Y.R.G Ctr, for AIDS Research and Education (11701) | Chennai | India |
| AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601) | Eldoret | 30100 | Kenya |
| Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501) | Kericho | 20200 | Kenya |
| College of Med. JHU CRS (30301) | Blantyre | Malawi |
| University of North Carolina Lilongwe CRS (12001) | Lilongwe | Malawi |
| Investigaciones Medicas en Salud (INMENSA) (11302) | San Isidro | Lima region | Peru |
| Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301) | Lima | 18 PE | Peru |
| CAPRISA eThekwini CRS (31422) | Durban | KwaZulu-Natal | 4011 | South Africa |
| Durban Adult HIV CRS (11201) | Durban | 4013 SF | South Africa |
| Soweto ACTG CRS (12301) | Johannesburg | South Africa |
| Univ. of Witwatersrand CRS (11101) | Johannesburg | South Africa |
| Chiang Mai University ACTG CRS (11501) | Chiang Mai | 50202 | Thailand |
| Joint Clinical Research Centre (JCRC) (12401) | Kampala | Uganda |
| Kalingalinga Clinic CRS (12801) | Lusaka | Zambia |
| UZ-Parirenyatwa CRS (30313) | Harare | Zimbabwe |
| FG001 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| TB Diagnosis Level at Entry | Number | participants |
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| Drug-Resistant TB Status at Entry | Number | participants |
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| Time to ART Start from Start of TB Medications | Median | Inter-Quartile Range | days |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percent of Participants Who Survived Without AIDS Progression. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Other Pre-specified | Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Other Pre-specified | Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Time to First New AIDS-defining Illness or Death. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | weeks | Through week 48 |
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| Secondary | Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. | All 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. | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | 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 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. | 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). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants With MTB IRIS. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants With HIV IRIS. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
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| Secondary | Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | 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. | Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy). | Posted | Number | 95% Confidence Interval | percent of participants | Through week 48 |
|
Through week 48
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 55 | 405 | 391 | 405 | ||
| EG001 | 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. | 44 | 401 | 389 | 401 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Peritonitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatitis alcoholic | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Meningitis bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Meningitis cryptococcal | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Meningitis tuberculous | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Mycobacterium avium complex infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pneumocystis jiroveci pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Tuberculoma of central nervous system | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Tuberculosis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral myocarditis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Gun shot wound | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Central nervous system mass | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Coma hepatic | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Encephalitis | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hemiplegia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Leukoplakia oral | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood albumin | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood albumin abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood bicarbonate abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Oropharyngeal plaque | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG ClinicalTrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, Inc. | (301) 628-3313 | ACTGCT.Gov@s-3.com |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Malawi |
|
| Brazil |
|
| Kenya |
|
| Peru |
|
| India |
|
| Zambia |
|
| Zimbabwe |
|
| Uganda |
|
| Botswana |
|
| Haiti |
|
| United States |
|
| Thailand |
|
| Probable TB |
|
| Not TB |
|
| Isoniazid (INH) Resistant TB |
|
| RIF and INH Resistant TB (Multi-Drug Resistant TB) |
|
| RIF and INH Sensitive TB |
|
| 8 |
The difference in percents was calculated as the percent failed in the Deferred ART arm minus the percent failed in the Immediate ART arm. |
| Superiority or Other |
| OG001 |
| 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. |
|
|
|
| OG001 | 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. |
|
|
|
| OG001 |
| 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. |
|
|
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. |
|
|
| 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. |
|
|
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.
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
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. |
|
|
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.
|
|
| OG001 | 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. |
|
|