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

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

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
Overall Participants Analyzed  [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)

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 ]

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 ]