REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment
Condition: HIV Infection
MeSH terms: Tuberculosis
Intervention: Atripla (r); Efavirenz; Truvada; Rifampin/isoniazid/pyrazinamide/ethambutol FDC; Rifampin/isoniazid FDC; Isoniazid
Intervention description: Patients are administered one tablet of Efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (EFV/FTC/TDF, Atripla) to taken be taken orally once daily at bedtime without food.; Participants will take one 600 mg tablet administered orally once daily without food.; Participants will take one tablet of Emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF, Truvada) administered orally once daily with or without food.; Participants will be administered Rifampin/isoniazid/pyrazinamide/ethambutol FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 of the protocol, for the first 8 weeks.; Participants will be administered rifampin/isoniazid FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 in the protocol, for 16 weeks following the first 8 weeks.; INH 300 mg orally once daily
Intervention MeSH terms: Efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Rifampin; Isoniazid; Pyrazinamide; Ethambutol; Isoniazid, pyrazinamide, rifampin drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 851.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      People with HIV have a high chance of becoming infected with TB, especially when they live in
      areas where TB infection is common. It can be difficult to diagnose TB in people who need to
      start HIV treatment right away. Within about 6 months after starting HIV treatment, some of
      these people can become very sick with TB and can even die from it.

      This study was being done in people who were starting HIV treatment and who lived in areas
      where the TB infection rate is high. The purpose of this study was to test an experimental
      approach to TB treatment to see if it is better than the usual approach. The experimental
      approach was to start TB treatment at the same time as HIV treatment, even when TB infection
      had not been found. The usual approach was to start TB treatment only if TB infection was
      found.

      In this study, half of the people started TB treatment at the same time as they started their
      HIV treatment. The other half started TB treatment only if TB infection was found.

      The study also tested how safe and effective it was to start TB treatment at about the same
      time as HIV treatment even when TB infection had not been found. The study collected
      information about diet, whether (and when) people in the study became sicker or died, how
      well their HIV was controlled, how they were feeling, how they were taking their medications,
      whether it mattered where they lived or what kind of HIV and TB care was standard, how many
      people were diagnosed with TB while in the study, and how the cost of the two treatment
      options on a national level could be compared.
    

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.