Isoniazid Preventive Therapy Among People With HIV and Heavy Alcohol Use in High Incidence Regions

Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH) worldwide and the risk is increased after starting antiretroviral therapy (ART). Isoniazid preventive therapy (IPT) is effective at reducing TB-related mortality but has long been contraindicated in patients with heavy alcohol use due to concerns for increased risk for hepatotoxicity. The World Health Organization recommends 36 months of empiric IPT—without diagnostic testing for latent TB infection—for all PLWH in resource-limited countries without symptoms of active TB. However, 36 months of empiric therapy is rarely completed. Using a Markov simulation model, researchers examined the risks and benefits of providing IPT for either 6 months or 36 months at the initiation of ART, compared with ART alone, among PLWH with heavy alcohol use. The model was validated in 3 high TB-/HIV-burden countries: Brazil, India, and Uganda.

• In India and Uganda, 6 months of IPT combined with ART extended life expectancy over both ART alone and 36 months of IPT combined with ART. In Brazil, ART alone was superior.
• Toxicity occurred in 160/1000 persons receiving 6 months of IPT and 415/1000 persons receiving 36 months of IPT, with fatal toxicity in 8/1000 receiving 6 months and 21/1000 receiving 36 months of IPT.

Comments: The risk-benefit ratio of IPT for PLWH with heavy alcohol use favored 6 months of therapy (over 36 months) in India and Uganda but not in Brazil where TB incidence is lower. Further studies should assess population-level risks and benefits in high-burden countries to inform refined guideline development.

Jeanette M. Tetrault, MD

Reference: Freiman JM, Jacobson KR, Muyindike WR, et al. Isoniazid preventive therapy for people with HIV who are heavy alcohol drinkers in high TB-/HIV-burden countries: a risk-benefit analysis. J Acquir Immune Defic Syndr. 2018;77(4):405–412.