Abstract

Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. The Immune Suppression Syndrome Clinic of Mbarara, Uganda. We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p<0.01). In multivariable analyses, those currently using alcohol had higher odds of elevated transaminases compared to those abstaining (aOR 1.65, 95% CI 1.15-2.37) as did males compared to females (aOR 2.68, 95% CI 1.90-3.78). Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Highlights

  • Tuberculosis (TB) is the leading cause of mortality for people living with HIV (PLWH) worldwide accounting for nearly one-third of all HIV deaths [1]

  • We evaluated the associations of current alcohol use and other variables of interest with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios and 95% confidence intervals (CI)

  • Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% had elevated transaminases pre-Isoniazid preventive therapy (IPT), with few (1.1%) severe ( 5X the upper limit of normal (ULN))

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Summary

Introduction

Tuberculosis (TB) is the leading cause of mortality for people living with HIV (PLWH) worldwide accounting for nearly one-third of all HIV deaths [1]. Through a Markov simulation model, that the benefits of 6 months of IPT outweigh the toxicity risks in PLWH who drink alcohol when given in high TB burden settings [8]. This model was based on limited data on the rate of liver toxicity in individuals receiving IPT. Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude “regular and heavy alcohol drinkers” from IPT.

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