Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir

AIDS. 2004 Nov 19;18(17):2277-84. doi: 10.1097/00002030-200411190-00008.

Abstract

Objective: To determine the incidence of significant liver enzyme elevations following the initiation of protease inhibitor (PI)-based antiretroviral therapy (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to define the role of chronic viral hepatitis in its development.

Design: Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART (indinavir, nelfinavir) that had at least one liver enzyme measurement before and during therapy.

Methods: The incidence of grade 3 and 4 liver enzyme elevations among persons with and without hepatitis B and/or C co-infection treated with PI-based ART were compared. Severe hepatotoxicity was defined as an increase in serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times an elevated baseline level.

Results: The incidence of grade 3 or 4 elevations among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%; indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800 mg/day), 17.2%. The risk was significantly greater among persons with chronic viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)-infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir, 86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity.

Conclusions: Our data suggest that the lopinavir/RTV is not associated with a significantly increased risk of hepatotoxity among HCV-infected and uninfected patients compared with an alternative PI-based regimen, nelfinavir. Accordingly, other medication-related factors (e.g, efficacy and non-hepatic toxicity) should guide individual treatment decisions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / immunology
  • Adult
  • Antiretroviral Therapy, Highly Active / methods*
  • Chronic Disease
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Protease Inhibitors / therapeutic use*
  • Hepatitis / immunology
  • Humans
  • Indinavir / therapeutic use
  • Liver / drug effects
  • Liver / enzymology*
  • Lopinavir
  • Male
  • Nelfinavir / therapeutic use
  • Prospective Studies
  • Pyrimidinones / therapeutic use
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Factors
  • Ritonavir / therapeutic use*
  • Saquinavir / therapeutic use
  • Treatment Outcome

Substances

  • HIV Protease Inhibitors
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Indinavir
  • Nelfinavir
  • Saquinavir
  • Ritonavir