title: Hepatotoxicity following nevirapine-containing regimens in HIV-1-infected individuals.
abstract: To determine the incidence of hepatotoxicity and to investigate whether plasma concentrations of nevirapine, in addition to other risk factors, could predict hepatotoxicity during treatment with nevirapine-containing regimens, we conducted a retrospective analysis with data from 174 individuals infected with human immunodeficiency virus-1 (HIV-1). During regular visits to the clinic, blood samples were collected for the determination of nevirapine plasma concentrations and clinical chemistry parameters including liver enzymes (LEs) and total bilirubin (TBR). Severe hepatotoxicity was defined as a grade > or =3 elevation in at least one of the tested LEs or TBR levels while on therapy. Analysis of predictive factors was focused on increases in aspartate aminotransferase (ASAT) and/or alanine aminotransferase (ALAT) to grade > or =2. Grade > or =3 elevation developed with an incidence of 0.15 per patient year (PY); only 3.4% of the patients developed grade > or =3 values for ASAT and/or ALAT (incidence 0.03 per PY). We found that patients who use a protease inhibitor (PI) in a nevirapine-containing regimen and patients who have chronic hepatitis B (HBV) infection are at a higher risk for the development of increases in ASAT and/or ALAT to grade > or =2. In contrast, the plasma concentration of nevirapine does not appear to be a predictive factor in this study population.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. apmod@slz.nl
authors.forename: Monique M R
authors.initials: MM
authors.lastname: De Maat
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathôt
authors.forename: Agnes I
authors.initials: AI
authors.lastname: Veldkamp
authors.forename: Aldwin D R
authors.initials: AD
authors.lastname: Huitma
authors.forename: Jan W
authors.initials: JW
authors.lastname: Mulder
authors.forename: Pieter L
authors.initials: PL
authors.lastname: Meenhorst
authors.forename: Eric C M
authors.initials: EC
authors.lastname: Van Gorp
authors.forename: Hilde
authors.initials: H
authors.lastname: Carlier
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin