Incidence, risk factors, and outcomes of anti-tuberculosis drug-induced hepatotoxicity in people with and without HIV in Thailand and the Philippines

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Abstract
Background: Anti-tuberculosis drug-induced hepatotoxicity (DIH) is a common complication among people living with HIV (PLWH), potentially leading to treatment interruptions. Objective: To determine the incidence of DIH and identify risk factors in Thai and Filipino PLWH on tuberculosis (TB) treatment, compared with those with TB mono-infection. Methods: We conducted a cohort study of Thai and Filipino adults with active TB using retrospective data from Thailand (2000–2024) and prospective data from the Philippines (2024). DIH was defined as AST or ALT ≥3 times the upper limit of normal. Logistic regression was used to assess DIH risk factors among PLWH; TB treatment outcomes were compared by DIH status. Results: Among 222 participants (138 PLWH, 84 HIV-negative), median age was 38 years, 63% were male, and median body mass index (BMI) was 18.2 kg/m 2 . DIH occurred in 13.8% of PLWH and 9.5% of HIV-negative individuals ( P = 0.35), with median onset at 10 and 3 weeks, respectively. Among PLWH, hepatitis C co-infection (aOR 5.84, 95% CI 1.51–22.55, P = 0.01) and lower BMI (aOR 0.78/kg/m 2 , 95% CI 0.63–0.97, P = 0.03) were independently associated with DIH. Dolutegravir use showed a non-significantly lower DIH risk (OR 0.51, 95%CI, 0.18 – 1.42). TB treatment success was similar between those with and without DIH (92.6% vs 90.3%); mortality was slightly higher with DIH (3.7% vs 1.5%). Conclusions: Hepatitis C co-infection and low BMI are key risk factors for DIH among PLWH receiving TB treatment. Despite these risks, DIH did not significantly impact treatment outcomes.

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