title: Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy.
abstract: This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART). Grade 4 LEE was defined as aminotransferase levels >10 times the upper limit of normal and >200 U above baseline levels. A multivariate Cox model was used to identify risk factors. The incidence of LEE was 6.3%. No patients died of LEE consequences. Risk factors were higher baseline alanine aminotransferase levels, chronic hepatitis B or C virus infection, antiretroviral therapy-naive patients undergoing their first HAART regimen, recent start of a regimen of nevirapine or high-dose ritonavir, and female sex. In hepatitis B virus (HBV)-coinfected patients, discontinuing lamivudine (3TC) use was a risk factor. In 97% of cases, >or=1 risk factor was present. In HBV-coinfected patients using 3TC, continued use of 3TC should be considered, even if 3TC-resistant HIV strains develop.
authors.affiliation: National AIDS Therapy Evaluation Center, Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, The Netherlands. f.w.wit@amc.uva.nl
authors.forename: Ferdinand W N M
authors.initials: FW
authors.lastname: Wit
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Jan
authors.initials: J
authors.lastname: Weel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000008:administration & dosage; D008111:Liver Function Tests; D008297:Male; D019829:Nevirapine / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects; D012737:Sex Factors; D000637:Transaminases / Q000032:analysis
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D000637:Transaminases; D000410:Alanine Transaminase; D019438:Ritonavir