Objective: To examine rates and predictors of severe hepatotoxicity with combination antiretroviral therapy in a developing country setting: the eight HIV-NAT randomized controlled trials in Thailand.
Methods: All patients (n = 692) received at least two nucleoside reverse transcriptase inhibitors; 215 also received a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 135 also received a protease inhibitor. Severe hepatotoxicity was defined as an increase in alanine aminotransferase (ALT) level to five times the upper limit of normal and an increase of at least 100 U/l from baseline. Liver function tests were available at baseline and weeks 4, 8, 12, 24, 36 and 48. Hepatitis B virus (HBV) and hepatitis C virus (HCV) testing was performed on stored serum.
Results: Mean age was 32.3 years; 52% were male, 11% had Centers for Disease Control and Prevention category C HIV disease at baseline, and 22% had received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV coinfection was 8.7%, 7.2%, and 0.4%, respectively. Incidence of severe hepatotoxicity was 6.1/100 person-years [95% confidence interval (CI), 4.3–8.3/100]. In multivariate analysis, predictors of severe hepatotoxicity were HBV or HCV coinfection, and NNRTI-containing therapy. Incidence of severe hepatotoxicity was particularly high among patients receiving nevaripine (18.5/100 person-years; 95% CI, 11.6–27.8) and nevirapine/efavirenz (44.4/100 person-years; 95% CI, 12.1–113.7).
Conclusions: Incidence and risk factors for severe hepatotoxicity appear similar among these Thai patients to those in other racial groups. Development of standardized antiretroviral therapy regimens for developing country settings should consider potential toxicity and capabilities for monitoring of toxicity.
From the aNational Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales, Sydney, Australia, the bHIV-Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand, the cInternational Antiviral Therapy Evaluation Centre (IATEC), University of Amsterdam, Amsterdam, the Netherlands and the dFaculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Requests for reprints to: Dr G. J. Dore, the National Centre in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria St, Darlinghurst, Sydney 2010, Australia.
Received: 17 February 2003; revised: 25 March 2003; accepted: 15 April 2003.