Background:
Isoniazid (INH) preventive therapy (IPT) reduces the incidence of TB disease among persons living with HIV (PWH). However, IPT deferral is suggested for persons with harmful alcohol use due to dual liver toxicity concerns.
Methods:
We conducted a single arm study evaluating liver toxicity rates of 6 months of IPT in PWH on antiretroviral therapy (ART) with latent TB (≥5 mm on tuberculin skin test) who reported either recent (prior 3 months) alcohol consumption (n=200) or no prior year alcohol consumption (n=101) at screening. Enrollment was limited to those with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN). Toxicity was detected by ALT, AST, and symptom monitoring. We defined Grade 3 or higher toxicity as ALT or AST ≥5 times the ULN or severe INH-related symptoms and stopped IPT upon detection. Grade 2 toxicities were defined as ALT or AST 2-5 times the ULN or moderate symptoms. We also examined the independent association of biomarker-confirmed alcohol use (none, low, medium, and high/very high, defined in Table), determined by the Alcohol Use Disorders Test – Consumption (AUDIT-C), modified to include the prior 3 months, and phosphatidylethanol (PEth), with Grade 3 or higher and Grade 2 toxicity.
Results:
Half (51.2%) of the participants were female, median age was 40 years (IQR 33-47), and 92.1% were virally suppressed. Twelve of 200 PWH reporting recent alcohol use (6.0%, 95% CI: 3.1-10.2) and 13/101 reporting no prior year alcohol use (12.9%, 95% CI: 7.0-21.0) experienced a Grade 3 or higher toxicity. Among those with no Grade 3 toxicity, 47/188 reporting recent alcohol use (25.0%, 95% CI: 19.0-31.8) and 13/87 reporting no prior year alcohol use (14.8%, 95% CI: 8.1-23.9) experienced at least one Grade 2 toxicity. We found no association between biomarker-confirmed alcohol use and Grade 3 or higher toxicity but did find an association of biomarker-confirmed alcohol use with Grade 2 toxicity (Table).
Conclusions:
Grade 3 or higher IPT toxicities among PWH with latent TB reporting recent alcohol use were infrequent. Biomarker confirmed alcohol use was not associated with having a Grade 3 or higher toxicity. Grade 2 toxicities were more common and high/very high-risk alcohol use was associated with their occurrence. Alcohol use does not appear to pose an increased risk for serious IPT toxicity among those without significant liver enzyme elevations at baseline ( < 2x ULN) in PWH on ART and should therefore not be deferred.
Adjusted odds ratios for the associations of biomarker-confirmed alcohol use with Grade 3 and higher toxicity and Grade 2 toxicity.