Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT)
Condition: Tuberculosis; HIV/AIDS; Alcohol Abuse
MeSH terms: Tuberculosis; Alcoholism
Intervention: Isoniazid 300 Mg ORAL TABLET; Pyridoxine 25 Mg Oral Tablet
Intervention description: The study intervention will include a single arm given (1) 6H: 300 mg INH daily by mouth for 6 months.; All participants will also receive 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months for the treatment duration to reduce the risk of INH-induced peripheral neuropathy.
Intervention MeSH terms: Pyridoxine; Vitamin B 6; Isoniazid
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adherence; Hepatotoxicity; Phosphatidtylethanol

Summary:

      The Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) will examine the safety
      and tolerability of, and adherence to, 6 months of daily INH (6H) in 300 TB and HIV-infected
      persons (200 drinkers and 100 non-drinkers) in Uganda. The first aim is to evaluate the
      safety and tolerability of 6H overall and by level of alcohol use. The second aim is to
      estimate adherence and compare adherence by level of alcohol use and at 3 and 6 months.
      Self-reported measures of alcohol use will be augmented by phosphatidylethanol (PEth), an
      established biomarker of alcohol use. Objective measures of adherence will include electronic
      pill bottle monitoring and a novel measure of INH exposure, INH concentration in hair. The
      study will actively monitor for hepatotoxicity using the U.S. standard of care for TB
      preventive therapy for heavy drinkers and discontinue if any Grade 3/4 toxicities are
      detected. The investigators will use the safety, tolerability, and adherence results,
      together with the known efficacy and mortality benefit of TB preventive therapy in
      HIV-infected persons in SSA, and an established decision analytic model of TB preventive
      therapy to conduct the third aim: to determine whether the benefits of TB preventive therapy
      outweigh the toxicity risks for HIV-infected drinkers in resource limited settings. The study
      will additionally follow the cohort every 6 months after completing INH to monitor drinking
      and the development of active TB.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > 18 years old

          2. Patient of the MRRH ISS Clinic

          3. HIV-infected

          4. Consume alcohol (self-reported consumption in the prior 3 months) (2/3) OR prior year
             non-drinker (1/3)

          5. Live within 2 hours of travel time to the ISS Clinic

          6. Fluent in either Runyankole or English

          7. No ALT/AST elevations (< = 2X ULN) confirmed by testing

          8. On ART for at least 6 months

          9. No history of active TB, TB treatment, or TB preventive therapy

         10. No probable current active TB as determined by symptom screening and followed by chest
             X-ray and Xpert MTB/RIF (if symptomatic)

         11. Positive TST results confirmed by testing

        Exclusion Criteria:

          1. Plans to move out of the catchment area within 6 months

          2. Probable TB via symptom screen and subsequent assessments

          3. History or current or past active TB, TB treatment, or TB preventive therapy

          4. ALT or AST >2x ULN

          5. Pregnant women