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

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Clinical Trials Group
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ethambutol; Isoniazid; Isoniazid, pyrazinamide, rifampin drug combination; Pyrazinamide; Rifampin; Tenofovir

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.