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

Sulkowski, Mark Sa; Mehta, Shruti Hb; Chaisson, Richard Ea; Thomas, David La,b; Moore, Richard Da,b

Clinical Science

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.

From the aDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, and the bDepartment of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland, USA.

Note Presented at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (Poster No. 1125). Boston, MA, October 24–28, 2003.

Correspondence to Mark S. Sulkowski, MD, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 448, Baltimore, Maryland 21287, USA.


Received: 9 April 2004; revised: 30 August 2004; accepted: 27 September 2004.

© 2004 Lippincott Williams & Wilkins, Inc.