HIV Infection, Tuberculosis
Conditions
Keywords
Treatment Naive, TB, HIV, Antiretroviral Agents, Strategy Study
Brief summary
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.
Detailed description
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.
Interventions
OTHERStrategy: Immediate ART
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.
OTHERStrategy: Deferred ART
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-infected. * Confirmed or probable TB (more information on the criterion can be found in the protocol). * Chest x-ray within 30 days prior to study entry. * Receipt of 1-14 cumulative days of rifampin- or other rifamycin-based TB treatment that was initiated within 28 days prior to study entry. * CD4 count less than 250 cells/mm\^3 within 30 days prior to study entry. * Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs. * Able to swallow oral medications. * Parent of guardian willing to provide informed consent, if applicable. * Karnofsky performance score =\>20 at time of study entry.
Exclusion criteria
* ART for longer than 7 cumulative days prior to study entry or treatment for any period of time with one or more antiretrovirals. Participants who have taken ART during pregnancy or for occupational exposure are not excluded. * Allergy or sensitivity to any of the study drugs or their formulations. * History of multidrug-resistant TB. * Receipt of any investigational therapy or chemotherapy within 30 days prior to study entry. * Certain medications. * Breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Who Survived Without AIDS Progression. | Through week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality | Through week 48 | 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. |
| Time to First New AIDS-defining Illness or Death. | Through week 48 | 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. |
| Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. | Through week 48 | 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. |
| Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. | Through week 48 | 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. |
| 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. | Through week 48 | 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. |
| Percent of Participants With HIV IRIS. | Through week 48 | 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. |
| Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | Through 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. |
| Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. | Through 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. |
| Percent of Participants With MTB IRIS. | Through week 48 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | Through week 48 | 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. |
| Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | Through week 48 | 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. |
Countries
Botswana, Brazil, Haiti, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, United States, Zambia, Zimbabwe
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 405 |
| 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. | 401 |
| Total | 806 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 31 | 37 |
| Overall Study | Lost to Follow-up | 27 | 19 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Immediate ART | Total | Deferred ART |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 403 Participants | 801 Participants | 398 Participants |
| Age, Continuous | 34 years | 34 years | 34 years |
| Drug-Resistant TB Status at Entry Isoniazid (INH) Resistant TB | 3 participants | 8 participants | 5 participants |
| Drug-Resistant TB Status at Entry Rifampin (RIF) Resistant TB | 1 participants | 1 participants | 0 participants |
| Drug-Resistant TB Status at Entry RIF and INH Resistant TB (Multi-Drug Resistant TB) | 1 participants | 5 participants | 4 participants |
| Drug-Resistant TB Status at Entry RIF and INH Sensitive TB | 400 participants | 792 participants | 392 participants |
| Region of Enrollment Botswana | 13 participants | 28 participants | 15 participants |
| Region of Enrollment Brazil | 57 participants | 113 participants | 56 participants |
| Region of Enrollment Haiti | 12 participants | 20 participants | 8 participants |
| Region of Enrollment India | 26 participants | 47 participants | 21 participants |
| Region of Enrollment Kenya | 36 participants | 72 participants | 36 participants |
| Region of Enrollment Malawi | 69 participants | 137 participants | 68 participants |
| Region of Enrollment Peru | 23 participants | 48 participants | 25 participants |
| Region of Enrollment South Africa | 109 participants | 221 participants | 112 participants |
| Region of Enrollment Thailand | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Uganda | 15 participants | 29 participants | 14 participants |
| Region of Enrollment United States | 9 participants | 19 participants | 10 participants |
| Region of Enrollment Zambia | 17 participants | 34 participants | 17 participants |
| Region of Enrollment Zimbabwe | 16 participants | 33 participants | 17 participants |
| Sex: Female, Male Female | 139 Participants | 305 Participants | 166 Participants |
| Sex: Female, Male Male | 266 Participants | 501 Participants | 235 Participants |
| TB Diagnosis Level at Entry Confirmed TB | 193 participants | 374 participants | 181 participants |
| TB Diagnosis Level at Entry Not TB | 4 participants | 6 participants | 2 participants |
| TB Diagnosis Level at Entry Probable TB | 208 participants | 426 participants | 218 participants |
| Time to ART Start from Start of TB Medications | 10 days | 14 days | 70 days |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 391 / 405 | 389 / 401 |
| serious Total, serious adverse events | 55 / 405 | 44 / 401 |
Outcome results
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants Who Survived Without AIDS Progression. | 13 percent of participants |
| Deferred ART | Percent of Participants Who Survived Without AIDS Progression. | 16 percent of participants |
Comparison: Assuming that immediate ART was better than deferred ART and that the combined rate in the deferred ART arm was 25% compared to 15% in the immediate ART arm (a 40% reduction), and assuming 10% loss to follow-up in a two-sided, two-sample 0.05-level asymptotically-normal test with 400 participants in each arm, there was 90% power. The percents tested were Kaplan-Meier estimators at week 48 with the associated Greenwood's variance.p-value: 0.4595.08% CI: [-2, 8]Z-test, 2-sided
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality | 44 percent of participants |
| Deferred ART | Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality | 47 percent of participants |
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.
Time frame: Through week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. | 9 percent of participants |
| Deferred ART | Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. | 10 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate ART | 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 |
| Immediate ART | 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 |
| Immediate ART | Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. | Dead | 8 percent of participants |
| Deferred ART | 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 |
| Deferred ART | 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 | 31 percent of participants |
| Deferred ART | Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. | Dead | 9 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate ART | 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 |
| Immediate ART | 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 |
| Immediate ART | Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | Dead | 8 percent of participants |
| Deferred ART | Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | HIV viral load < 400 copies/mL | 75 percent of participants |
| Deferred ART | 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 | 16 percent of participants |
| Deferred ART | Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. | Dead | 9 percent of participants |
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.
Time frame: Through week 48
Population: 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).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate ART | 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 |
| Immediate ART | 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 |
| Immediate ART | 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 |
| Immediate ART | 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 |
| Deferred ART | 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 | 6 percent of participants |
| Deferred ART | 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 | 82 percent of participants |
| Deferred ART | 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 | 7 percent of participants |
| Deferred ART | 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 | 5 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. | 12 percent of participants |
| Deferred ART | Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. | 17 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants With HIV IRIS. | 3 percent of participants |
| Deferred ART | Percent of Participants With HIV IRIS. | 3 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants With MTB IRIS. | 11 percent of participants |
| Deferred ART | Percent of Participants With MTB IRIS. | 5 percent of participants |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate ART | Time to First New AIDS-defining Illness or Death. | 5th percentile | 4 weeks |
| Immediate ART | Time to First New AIDS-defining Illness or Death. | 10th percentile | 13 weeks |
| Deferred ART | Time to First New AIDS-defining Illness or Death. | 5th percentile | 7 weeks |
| Deferred ART | Time to First New AIDS-defining Illness or Death. | 10th percentile | 12 weeks |
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | 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 |
| Deferred ART | Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 10 percent of participants |
Comparison: The study was not powered for this pre-specified subgroup analysis.p-value: 0.6795.08% CI: [-7, 4]Z-test, 2-sided
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.
Time frame: Through week 48
Population: Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate ART | Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 16 percent of participants |
| Deferred ART | Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression. | 27 percent of participants |
Comparison: The study was not powered for this pre-specified subgroup analysis.p-value: 0.0295.08% CI: [2, 21]Z-test, 2-sided