No increased risk of hepatotoxicity in long-term use of nonnucleoside reverse transcriptase inhibitors in HIV-infected patients

HIV Med. 2012 Aug;13(7):448-52. doi: 10.1111/j.1468-1293.2012.00995.x. Epub 2012 Mar 14.

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.

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects*
  • Benzoxazines / administration & dosage
  • Benzoxazines / adverse effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Chemical and Drug Induced Liver Injury / etiology
  • Child
  • Coinfection
  • Cyclopropanes
  • Female
  • Hepatitis C / blood
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Reverse Transcriptase Inhibitors
  • efavirenz