Risk factors for severe hepatic injury after introduction of highly activeantiretroviral therapy

Objectives: Treatment of HIV infection with highly antiretroviral therapy ( HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known. Patients and Methods: Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as grea ter than or equal to3.5-fold rise above abnormal baseline values. Results: Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepati tis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patient s received protease inhibitors (Pls), 90 received nonnucleoside reverse tra nscriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. S evere hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. B oth univariate and multivariate analyses identified alcohol abuse, HCV coin fection, and older age as independent risk factors. Predictor variables in the final multivariate model were alcohol abuse (risk ratio [RR], 5.87 95%, confidence interval [CI], 1.49-23.15; p = .01), positive HCV serology (RR, 3.99 95% CI, 1.32-12.10; p = .01), and older age (RR, 1.11; 95% CI, 1.04-1 .18; p = 0.001). Conclusions: Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcoho l abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chro nic HCV infection should be considered.