Immediate Versus Deferred Start of Anti-HIV Therapy in HIV-Infected Adults Being Treated for Tuberculosis (STRIDE)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00108862
First received: April 19, 2005
Last updated: July 9, 2012
Last verified: July 2012
Results First Received: September 27, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infection
Tuberculosis
Interventions: Other: Strategy: Immediate ART
Other: Strategy: Deferred ART

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Immediate ART     Deferred ART  
STARTED     405     401 [1]
COMPLETED     337     339  
NOT COMPLETED     68     62  
Death                 31                 37  
Withdrawal by Subject                 10                 6  
Lost to Follow-up                 27                 19  
[1] Three participants who were deemed clinically ineligible and taken off study were omitted.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    Immediate ART     Deferred ART     Total  
Number of Participants  
[units: participants]
  405     401     806  
Age  
[units: participants]
     
<=18 years     0     2     2  
Between 18 and 65 years     403     398     801  
>=65 years     2     1     3  
Age  
[units: years]
Median ( Inter-Quartile Range )
  34  
  ( 29 to 40 )  
  34  
  ( 29 to 42 )  
  34  
  ( 29 to 41 )  
Gender  
[units: participants]
     
Female     139     166     305  
Male     266     235     501  
Region of Enrollment  
[units: participants]
     
South Africa     109     112     221  
Malawi     69     68     137  
Brazil     57     56     113  
Kenya     36     36     72  
Peru     23     25     48  
India     26     21     47  
Zambia     17     17     34  
Zimbabwe     16     17     33  
Uganda     15     14     29  
Botswana     13     15     28  
Haiti     12     8     20  
United States     9     10     19  
Thailand     3     2     5  
TB Diagnosis Level at Entry  
[units: participants]
     
Confirmed TB     193     181     374  
Probable TB     208     218     426  
Not TB     4     2     6  
Drug-Resistant TB Status at Entry  
[units: participants]
     
Rifampin (RIF) Resistant TB     1     0     1  
Isoniazid (INH) Resistant TB     3     5     8  
RIF and INH Resistant TB (Multi-Drug Resistant TB)     1     4     5  
RIF and INH Sensitive TB     400     392     792  
Time to ART Start from Start of TB Medications  
[units: days]
Median ( Inter-Quartile Range )
  10  
  ( 7 to 12 )  
  70  
  ( 66 to 75 )  
  14  
  ( 10 to 70 )  



  Outcome Measures
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1.  Primary:   Percent of Participants Who Survived Without AIDS Progression.   [ Time Frame: Through week 48 ]

2.  Secondary:   Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality   [ Time Frame: Through week 48 ]

3.  Secondary:   Time to First New AIDS-defining Illness or Death.   [ Time Frame: Through week 48 ]

4.  Secondary:   Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression.   [ Time Frame: Through week 48 ]

5.  Secondary:   Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity.   [ Time Frame: Through week 48 ]

6.  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.   [ Time Frame: Through week 48 ]

7.  Secondary:   Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48.   [ Time Frame: Through week 48 ]

8.  Secondary:   Percent of Participants With MTB IRIS.   [ Time Frame: Through week 48 ]

9.  Secondary:   Percent of Participants With HIV IRIS.   [ Time Frame: Through week 48 ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Percent of Participants With HIV IRIS.
Measure Description 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the intent-to-treat approach (i.e., ignoring changes from randomized treatment strategy).

Reporting Groups
  Description
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.

Measured Values
    Immediate ART     Deferred ART  
Number of Participants Analyzed  
[units: participants]
  405     401  
Percent of Participants With HIV IRIS.  
[units: percent of participants]
Number ( 95% Confidence Interval )
  3  
  ( 2 to 5 )  
  3  
  ( 1 to 5 )  

No statistical analysis provided for Percent of Participants With HIV IRIS.



10.  Secondary:   Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.   [ Time Frame: Through week 48 ]

11.  Other Pre-specified:   Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.   [ Time Frame: Through week 48 ]

12.  Other Pre-specified:   Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.   [ Time Frame: Through week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
None.


  More Information