Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART

Background: Highly active antiretroviral therapy (HAART) is strongly effect ive in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determin ants of severe hepatotoxicity in a clinical setting are still sparse. Methods: This is a prospective study of HIV-1-positive individuals with kno wn HBsAg and HCV-Ab serology. The study end point was progression to alanin e aminotransferase (ALT) levels greater than or equal to 200 IU/L after HAA RT initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. Results: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injectio n drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individual s progressed to tile end point with a probability of 7.9% (95% confidence i nterval [CI], 5.6-10.0) of progression at 24 months from starting. Independ ent factors predicting progression to the end point were baseline ALT level s (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (H R, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.0 4-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% Cl, 0.12 -0.71). Conclusions: There was a low risk of ALT greater than or equal to 200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART ini tiation are important predictors of progression to ALT greater than or equa l to 200 IU/L; stavudine-containing regimens were associated with a lower r isk compared with zidovudine-containing regimens.