title: No increased risk of hepatotoxicity in long-term use of nonnucleoside reverse transcriptase inhibitors in HIV-infected patients.
abstract: OBJECTIVE
  The aim of this study was to assess the incidence of hepatotoxicity in patients who had used nonnucleoside reverse transcriptase inhibitors (NNRTIs) for at least 3 years.
  
  
  METHODS
  The study group consisted of HIV-infected patients under follow-up at our clinic, who had continuously used an NNRTI-containing regimen (efavirenz or nevirapine) for at least 3 years. Patients who had used protease inhibitors (PIs) for the same time span constituted a control group. Hepatotoxicity was graded according to the modified AIDS Clinical Trial Group grading system, using alanine aminotransferase (ALT) as a marker.
  
  
  RESULTS
  One hundred and twenty-two patients on an NNRTI regimen and 54 PI-using patients were included in the analysis. The mean follow-up time was nearly 6 years. Eighteen NNRTI-using patients (14.8%) developed a clinically relevant (≥  grade II) event of hepatotoxicity during treatment; five of them (4.1%) developed severe hepatotoxicity (≥  grade III). No significant difference in the hepatotoxicity rate was seen between NNRTI- and PI-using patients (14.8 vs. 18.5%, respectively; P = 0.52) or between patients using efavirenz and nevirapine (13.8% vs. 16.7%, respectively; P = 0.51). A hepatitis C virus (HCV) coinfection was associated with an increased risk of the development of hepatotoxicity during NNRTI therapy [odds ratio (OR) 1.83; 95% confidence interval (CI) 1.33-4.24; P < 0.01]. Finally, we observed that more hepatotoxic events occurred during the first year of NNRTI therapy compared with the entire period after 1 year (6.6 vs. 2.8 events, respectively, per 100 person-years of treatment; P = 0.04).
  
  
  CONCLUSIONS
  Long-term NNRTI use was not associated with a higher risk of clinically significant liver toxicity in patients who had been treated with NNRTI for at least 3 years.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bj
authors.initials: B
authors.lastname: Van Welzen
authors.forename: T
authors.initials: T
authors.lastname: Mudrikova
authors.forename: Je
authors.initials: J
authors.lastname: Arends
authors.forename: Aim
authors.initials: A
authors.lastname: Hoepelman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D002648:Child; D060085:Coinfection; D003521:Cyclopropanes; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz