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

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/mm3 obtained within 45 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
• 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.
• Males and females age >/= 13 years.
• 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 (see list in A5274/REMEMBER MOPS, section 3.2.1) 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.