Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients

J Antimicrob Chemother. 2011 Nov;66(11):2605-14. doi: 10.1093/jac/dkr357. Epub 2011 Sep 7.

Abstract

Objectives: To compare the frequency of grade 3 or 4 transaminase elevations (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three-antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis or cirrhosis.

Patients and methods: All pre-treated or treatment-naive HIV/HCV co-infected patients who started an antiretroviral regimen including two nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in seven Spanish centres from January 2007 to December 2009 were included in this prospective study.

Results: Of 262 patients included in this study, 76 (29%) individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%) a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2-23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%) subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P = 0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5 (9.3%), respectively (P = 0.931).

Conclusions: The frequency of grade 3-4 TEs associated with efavirenz-based ART combinations under clinical practice conditions is low and similar to that found in patients receiving PI/r currently used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have an impact on the development of TEs caused by these antiretroviral drugs in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Benzoxazines / administration & dosage
  • Benzoxazines / adverse effects*
  • Benzoxazines / therapeutic use
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Coinfection
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects
  • Hepacivirus / drug effects
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy
  • Humans
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects*
  • Ritonavir / therapeutic use
  • Transaminases / blood

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • HIV Protease Inhibitors
  • Transaminases
  • efavirenz
  • Ritonavir