Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use: a single arm trial

Abstract

Objective: Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption. Design: A prospective study of PWH receiving INH. Methods: We included PWH in southwest Uganda with recent (prior 3 months) (n = 200) or no (prior year) self-reported alcohol consumption (n = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2× or less the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST at least 5× the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2–5× the ULN or moderate symptoms. Results: The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% [95% confidence interval (95% CI) 5.4–12.0]; all resolved after INH cessation. Incidence was 6.0% (95% CI 3.1–10.2) among those reporting recent alcohol use and 12.9% (95% CI 7.0–21.0) among those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI 17.0–27.1); 25.0% (95% CI 19.0–31.8) among those with recent alcohol use and 14.8% (95% CI 8.1–23.9) among those with no prior year alcohol use. Conclusion: Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN).

Psychometric assessment of the Runyankole-translated Marlowe-Crowne Social Desirability Scale among persons with HIV in Uganda

“…This analysis used pooled baseline data from studies in Uganda, namely the Drinkers’ Intervention to Prevent Tuberculosis (TB, DIPT, Clinical Trials Registry NCT03492216 [Date of Registration: May 2018]) randomized controlled trial (RCT) [ 27 ], the Mobile Technology to Extend Clinic-Based Counseling for HIV + s in Uganda (Extend, Clinical Trials Registry NCT03928418 [Date of Registration: April 2019]) RCT [ 28 ], and the Alcohol Drinkers’ Exposure to Preventive Therapy for TB (ADEPT-T) observational study [ 29 ].…”

“…The ADEPT-T study was conducted between 2017 and 2020 and aimed to determine the incidence of isoniazid-related toxicity among PWH who consume alcohol and whether the rate of isoniazid-related toxicity varied by quantity of alcohol consumption ( N = 301) [ 29 ]. Details pertaining to recruitment and screening procedures have been published elsewhere [ 29 ]. Participants were provided a 6-month course of isoniazid and pyridoxine (B6), completed questionnaires and provided blood samples at baseline and follow-up visits.…”