title: Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996-2001.
abstract: 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.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
authors.forename: W Phillip
authors.initials: WP
authors.lastname: Law
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Duncombe
authors.forename: Apicha
authors.initials: A
authors.lastname: Mahanontharit
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boyd
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D048588:Benzoxazines; D056486:Chemical and Drug Induced Liver Injury; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D006509:Hepatitis B / Q000139:chemically induced / Q000453:epidemiology; D006526:Hepatitis C / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000453:epidemiology; D008297:Male; D019829:Nevirapine / Q000009:adverse effects; D010078:Oxazines / Q000009:adverse effects; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz