Trial Outcomes & Findings for REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment (NCT NCT01380080)

Last Updated: 2024-10-15

Results Overview

The Kaplan-Meier estimate of the cumulative probability of death or unknown vital status by week 24. The vital status was considered unknown at week 24 if a participant prematurely discontinued from the study before week 24 and no vital status was obtained at week 48.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

851 participants

Primary outcome timeframe

From study entry to week 24

Results posted on

2024-10-15

Participant Flow

Recruited at AIDS Clinical Trials Units in 10 international countries. Recruitment occurred between October 31, 2011 (date of first participant was randomized) and June 9, 2014 (date of last participant was randomized).

851 were randomized 1:1 to treatment strategies A and B. Results reported for 850 eligible participants; 1 was subsequently found ineligible and excluded from all analyses.

Participant milestones

Participant milestones
Measure	Arm A: Empiric Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Study STARTED	424	426
Overall Study COMPLETED	339	343
Overall Study NOT COMPLETED	85	83

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Empiric Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Study Death	36	44
Overall Study Site is closing	28	31
Overall Study Not able to get to clinic	7	1
Overall Study Not willing to adhere to requirements	6	2
Overall Study Withdrawal by Subject	5	2
Overall Study Lost to Follow-up	3	3

Baseline Characteristics

REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).	Total n=850 Participants Total of all reporting groups
Age, Continuous	36 years n=5 Participants	35 years n=7 Participants	36 years n=5 Participants
Sex: Female, Male Female	200 Participants n=5 Participants	200 Participants n=7 Participants	400 Participants n=5 Participants
Sex: Female, Male Male	224 Participants n=5 Participants	226 Participants n=7 Participants	450 Participants n=5 Participants
Race/Ethnicity, Customized Black Non-Hispanic	375 Participants n=5 Participants	384 Participants n=7 Participants	759 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	32 Participants n=5 Participants	29 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Asian, Pacific Islander	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Haiti	53 Participants n=5 Participants	56 Participants n=7 Participants	109 Participants n=5 Participants
Region of Enrollment Malawi	95 Participants n=5 Participants	98 Participants n=7 Participants	193 Participants n=5 Participants
Region of Enrollment Brazil	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment South Africa	86 Participants n=5 Participants	90 Participants n=7 Participants	176 Participants n=5 Participants
Region of Enrollment Zimbabwe	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment Uganda	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment Zambia	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment Kenya	77 Participants n=5 Participants	75 Participants n=7 Participants	152 Participants n=5 Participants
Region of Enrollment Peru	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment India	17 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants
HIV-1 RNA	5.4 log10 copies/mL n=5 Participants	5.3 log10 copies/mL n=7 Participants	5.3 log10 copies/mL n=5 Participants
CD4+ T-cell count	18 cells/mm^3 n=5 Participants	19 cells/mm^3 n=7 Participants	18 cells/mm^3 n=5 Participants

PRIMARY outcome

Timeframe: From study entry to week 24

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Cumulative Probability of Death or Unknown Vital Status by Week 24	5.2 Cumulative probability per 100 persons Interval 3.5 to 7.8	5.2 Cumulative probability per 100 persons Interval 3.4 to 7.8

SECONDARY outcome

Timeframe: From study entry to week 24

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

The Kaplan-Meier estimate of cumulative probability of death by week 24

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Cumulative Probability of Death by Week 24	4.8 Cumulative probability per 100 persons Interval 3.1 to 7.3	5.2 Cumulative probability per 100 persons Interval 3.4 to 7.8

SECONDARY outcome

Timeframe: From study entry to week 96

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

The Kaplan-Meier estimate of the cumulative probability of first AIDS progression which was defined as the identification of a new World Health Organization (WHO) stage 3 or 4 condition

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Cumulative Probability of First AIDS Progression by Week 96	16.6 Cumulative probability per 100 persons Interval 13.3 to 20.6	11.3 Cumulative probability per 100 persons Interval 8.6 to 14.8

SECONDARY outcome

Timeframe: From study entry to week 24

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

The Kaplan-Meier estimate of the cumulative probability of death or AIDS progression by week 24. AIDS progression was defined as new WHO stage 3 or 4 conditions occurred after study entry.

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Cumulative Probability of Death or AIDS Progression by Week 24	17.1 Cumulative probability per 100 persons Interval 13.9 to 21.1	12.5 Cumulative probability per 100 persons Interval 9.7 to 16.0

SECONDARY outcome

Timeframe: At weeks 0, 4, 24, and 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completed at random.

Proportion of participants with HIV-1 RNA level \<400 copies/mL.

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL Week 0	0 Proportion of participants Interval 0.0 to 0.02	0.01 Proportion of participants Interval 0.0 to 0.03
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL Week 4	0.46 Proportion of participants Interval 0.41 to 0.51	0.49 Proportion of participants Interval 0.44 to 0.55
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL Week 24	0.84 Proportion of participants Interval 0.79 to 0.87	0.85 Proportion of participants Interval 0.81 to 0.89
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL Week 48	0.87 Proportion of participants Interval 0.83 to 0.9	0.89 Proportion of participants Interval 0.86 to 0.92

SECONDARY outcome

Timeframe: At weeks 0, 4, 24, and 48

Population: Intent to treat: All eligible participants were included in the analysis: Participants were analyzed per original assigned randomized treatment. Missing data were assigned missing completely at random.

The absolute levels of CD4+ T-cell counts (cells/mm\^3)

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
CD4+ T-cell Count Week 0	18 cells/ mm^3 Interval 9.0 to 31.0	19 cells/ mm^3 Interval 9.0 to 33.0
CD4+ T-cell Count Week 4	74 cells/ mm^3 Interval 37.0 to 118.0	76 cells/ mm^3 Interval 41.0 to 123.0
CD4+ T-cell Count Week 24	121 cells/ mm^3 Interval 75.0 to 172.0	121 cells/ mm^3 Interval 80.0 to 188.0
CD4+ T-cell Count Week 48	176 cells/ mm^3 Interval 112.0 to 251.0	172 cells/ mm^3 Interval 112.0 to 245.0

SECONDARY outcome

Timeframe: Weeks 0, 4, 24 and 48

Population: Intention to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completely at random.

Change was calculated as the CD4+ T-cell count at the later weeks (4, 24 and 48) minus the baseline (week 0) CD4+ T-cell count.

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
CD4+ T-cell Count Change From Baseline Week 4	49 cells/ mm^3 Interval 20.0 to 91.0	54 cells/ mm^3 Interval 22.0 to 94.0
CD4+ T-cell Count Change From Baseline Week 24	96 cells/ mm^3 Interval 55.0 to 147.0	102 cells/ mm^3 Interval 60.0 to 159.0
CD4+ T-cell Count Change From Baseline Week 48	158 cells/ mm^3 Interval 92.0 to 224.0	146 cells/ mm^3 Interval 90.0 to 219.0

SECONDARY outcome

Timeframe: From study entry to week 96

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Median time to TB treatment initiation since study entry

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Time to Initiation of TB Treatment by Week 96	0 Days Interval 0.0 to 1.0	0 Days Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: From study entry to week 96

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with TB diagnosis per current ACTG Diagnosis Appendix 60 by week 96

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With TB Diagnosis by Week 96	0.08 Proportion of participants	0.05 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with at least one new Grade 3 or 4 laboratory or sign or symptom that is at least a one-grade increase from baseline by Week 48. Grade 3=Severe, Grade 4=Life-Threatening according to DAIDS AE Grading Table (see references).

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With at Least One New Grade 3 or 4 Adverse Event That is at Least a One-grade Increase From Baseline by Week 48	0.32 Proportion of participants	0.30 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48. The lab events were collected at study entry, weeks 2, 4, 8, 12, 16, 20, 24, and 48.

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with at least one new Grade 3 or 4 that is at least a one-grade increase from baseline for the following targeted laboratory values by Week 48 The targeted laboratory events include hemoglobin, serum creatinine, ALT and AST

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With at Least One New Grade 3 or 4 Targeted Laboratory Value That is at Least a One-grade Increase From Baseline by Week 48	0.11 Proportion of participants	0.13 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with IRIS (using current ACTG definition Appendix 60, see References) by Week 48. IRIS in participants with TB and other opportunistic infections may occur shortly after the initiation of potent combination ART, particularly in participants with advanced HIV disease.

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48	0.04 Proportion of participants	0.05 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with reportable hospitalization reported by Week 48

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants With Reportable Hospitalization by Week 48	0.10 Proportion of participants	0.12 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with premature discontinuation of any component of TB treatment by Week 48

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants Who Prematurely Discontinued Any Component of TB Treatment by Week 48	0.13 Proportion of participants	0.05 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment

Proportion of participants with premature discontinuation of antiretroviral therapy (ART) by Week 48

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48	0.19 Proportion of participants	0.21 Proportion of participants

SECONDARY outcome

Timeframe: From study entry to week 48

Population: Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment.

The Kaplan-Meier estimate of the cumulative probability of death or AIDS progression by week 48. AIDS progression was defined as new WHO stage 3 or 4 conditions occurred after study entry.

Outcome measures

Outcome measures
Measure	Arm A: Empiric n=424 Participants Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 Participants Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Cumulative Probability of Death or AIDS Progression by Week 48	19.3 Cumulative probability per 100 persons Interval 15.8 to 23.4	15.3 Cumulative probability per 100 persons Interval 12.2 to 19.1

Adverse Events

Arm A: Empiric

Serious events: 85 serious events

Other events: 380 other events

Deaths: 36 deaths

Arm B: IPT

Serious events: 94 serious events

Other events: 379 other events

Deaths: 44 deaths

Serious adverse events

Other adverse events

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social & Scientific Systems, Inc.

Phone: (301) 628-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm A: Empiric n=424 participants at risk Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only	Arm B: IPT n=426 participants at risk Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Gastrointestinal disorders Abdominal pain	6.6% 28/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	6.1% 26/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Gastrointestinal disorders Diarrhoea	9.9% 42/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	8.0% 34/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Gastrointestinal disorders Nausea	5.2% 22/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	5.2% 22/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Gastrointestinal disorders Vomiting	9.2% 39/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	12.0% 51/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
General disorders Pyrexia	10.8% 46/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	12.9% 55/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Infections and infestations Oral candidiasis	11.6% 49/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	11.5% 49/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Infections and infestations Pulmonary tuberculosis	5.2% 22/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	3.1% 13/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Alanine aminotransferase increased	13.7% 58/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	17.6% 75/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Aspartate aminotransferase increased	23.3% 99/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	23.7% 101/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood albumin decreased	35.6% 151/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	37.3% 159/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood alkaline phosphatase increased	8.5% 36/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	10.1% 43/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood bicarbonate decreased	15.6% 66/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	16.9% 72/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood creatinine increased	5.9% 25/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	10.6% 45/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood potassium decreased	7.5% 32/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	7.3% 31/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood sodium decreased	34.0% 144/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	32.9% 140/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Haemoglobin decreased	28.1% 119/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	22.3% 95/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Neutrophil count decreased	38.0% 161/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	38.3% 163/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Platelet count decreased	7.5% 32/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	8.9% 38/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Weight decreased	8.0% 34/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	5.9% 25/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations White blood cell count decreased	32.1% 136/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	30.5% 130/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Nervous system disorders Headache	6.4% 27/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	10.1% 43/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Reproductive system and breast disorders Vaginal discharge	5.2% 22/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	2.3% 10/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Cough	9.7% 41/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	11.3% 48/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Oropharyngeal plaque	10.1% 43/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	7.5% 32/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Blood and lymphatic system disorders Anaemia	5.0% 21/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	5.2% 22/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
General disorders Chest pain	4.2% 18/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	5.2% 22/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Infections and infestations Pneumonia bacterial	5.4% 23/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	4.9% 21/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Investigations Blood sodium increased	5.2% 22/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	3.3% 14/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Skin and subcutaneous tissue disorders Pruritus	4.2% 18/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	5.4% 23/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Skin and subcutaneous tissue disorders Rash	5.0% 21/424 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.	7.3% 31/426 • From treatment dispensation to up to week 96 The protocol required reporting of signs and symptoms and laboratory abnormalities of \>=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.