Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients

J Infect Dis. 2007 Sep 1;196(5):670-6. doi: 10.1086/520092. Epub 2007 Jul 13.


Background: The risk of liver toxicity during antiretroviral drug use in human immunodeficiency virus (HIV)-positive patients increases in the presence of chronic hepatitis C virus (HCV) infection. It is unknown whether sustained HCV clearance after interferon (IFN)-based therapy might reduce this complication.

Methods: The incidence of severe elevations in liver enzyme levels during antiretroviral therapy was retrospectively analyzed in a group of HIV/HCV-coinfected patients after completion of a full course of IFN-based therapy. Hepatic events were recorded according to the achievement of a sustained virological response (SVR), and the presence of advanced liver fibrosis was assessed by transient elastometry.

Results: A total of 132 HIV/HCV-coinfected patients were analyzed (66% men; mean age, 38 years). Overall, 33% achieved an SVR and 40% had advanced liver fibrosis after IFN therapy. A total of 49 episodes of liver toxicity occurred during a mean of 35 months of follow-up (9.7% per year) after IFN therapy. The yearly incidence of hepatic events was greater in patients who did not achieve an SVR than in those who did (12.9% vs. 3.1%; P<.001) and in patients with advanced liver fibrosis than in those without it (14.4% vs. 7.6%; P=.003). Drugs involved in hepatic events were dydeoxynucleoside analogues (namely, didanosine and stavudine; 40%) nevirapine (30%), efavirenz (11%), and protease inhibitors (PIs; 8%). In logistic regression analysis, lack of an SVR (odds ratio [OR], 6.13 [95% confidence interval {CI}, 1.83-37.45]; P=.003) and the use of dydeoxynucleosides (OR, 3.59 [95% CI, 1.23-10.42]; P=.02) were independent predictors of hepatotoxicity after IFN therapy. Conversely, regimens containing PIs (OR, 0.07 [95% CI, 0.02-0.30]; P<.01) or efavirenz (OR, 0.13 [95% CI, 0.04-0.44]; P=.001) were associated with a diminished risk of hepatic events.

Conclusion: Sustained HCV clearance after IFN-based therapy reduces the risk of liver toxicity during antiretroviral therapy, which should further encourage the treatment of chronic hepatitis C in HIV-coinfected patients. In this population, prescription of PIs or efavirenz decreases and use of dydeoxynucleoside analogues increases the risk of hepatotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis
  • Male
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins
  • Ribavirin / therapeutic use


  • Anti-Retroviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a