REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment (REMEMBER)
HIV Infection
About this trial
This is an interventional treatment trial for HIV Infection
Eligibility Criteria
Inclusion Criteria:
- HIV-1 infection
- Willingness to start efavirenz-based ART as soon as possible and within no more than 3 days following randomization.
- CD4+ cell count <50 cells/mm^3 obtained within 45 days prior to study entry
- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and total bilirubin ≤ 2.5 X ULN within 30 days prior to study entry.
- Creatinine clearance ≥30 mL/min either measured or estimated using values obtained within 30 days prior to study entry.
- Results from a hepatitis B surface antigen test performed within 30 days prior to study entry.
- Agreement not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
- Female candidates of reproductive potential must have a negative serum or urine (15-25 mIU/mL) pregnancy test result within 7 days prior to study entry.
- Female candidates of reproductive potential who are participating in sexual activity that could lead to pregnancy must use two reliable methods of contraception while on study.
- Karnofsky performance score >/= 30 at time of study entry.
- Ability to swallow medications.
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
- Intention to remain in the same general geographic region for the duration of study participation.
Exclusion Criteria:
- Presence of any confirmed or probable TB based on criteria listed in the current ACTG diagnosis appendix within 30 days prior to study entry and following completion of study-specific screening algorithm.
- Use of single-dose NVP for prevention of mother-to-child transmission (pMTCT) within 24 months prior to study entry.
- Use of prohibited medications within 30 days prior to study entry.
- Known allergy/sensitivity or any hypersensitivity to components of study-required ART or TB treatment.
- Current receipt of treatment for active TB or receipt of >14 days cumulative treatment for active TB within 96 weeks prior to study entry.
- Receipt of >30 days cumulative of INH prophylaxis within 48 weeks prior to study entry.
- Receipt at any time prior to study entry of >7 days cumulative treatment with any ARV or combination of ARVs (except for ARVs taken for any length of time during pregnancy for pMTCT, or ARVs taken for occupational exposure).
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Current Grade ≥2 neuropathy.
- History of multi-drug-resistant (MDR) TB.
- Within 12 weeks prior to entry, exposure to a household member or co-worker with known MDR TB.
Sites / Locations
- Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
- GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
- Les Centres GHESKIO CRS
- YRG CARE Medical Ctr., VHS Chennai CRS
- BJ Medical College CRS
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS
- College of Med. JHU CRS (30301)
- University of North Carolina Lilongwe CRS (12001)
- San Miguel CRS
- Barranco CRS (11301)
- Wits HIV CRS
- CAPRISA eThekwini CRS
- Durban Adult HIV CRS
- Soweto ACTG CRS (12301)
- Joint Clinical Research Centre (JCRC) (12401)
- Kalingalinga Clinic CRS (12801)
- UZ-Parirenyatwa CRS
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A: Empiric
Arm B: IPT
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
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).