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JAC Advance Access originally published online on January 23, 2009
Journal of Antimicrobial Chemotherapy 2009 63(3):579-584; doi:10.1093/jac/dkn531
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or C

Jean-Luc Meynard1,*, Karine Lacombe1, Jean-Marie Poirier2, Jennifer Legrand3, Laurence Morand-Joubert4 and Pierre-Marie Girard1

1 Service des Maladies Infectieuses et Tropicales, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France 2 Service de Pharmacologie, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France 3 Service de Pharmacie, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, France 4 Service de Bactériologie-Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France

Received 6 August 2008; returned 12 September 2008; revised 9 December 2008; accepted 12 December 2008

* Corresponding author. E-mail: jean-luc.meynard{at}sat.ap-hop-paris.fr

Objectives: Liver function is a key component of efavirenz metabolism and might be altered in severe liver fibrosis induced by HIV/chronic hepatitis co-infection. However, data evaluating the impact of liver fibrosis stages on the plasma efavirenz level are lacking.

Patients and methods: In this study, conducted in 134 HIV-infected patients [77, 35 and 22 HIV mono-infected, HIV/hepatitis C virus (HCV) co-infected and HIV/hepatitis B virus (HBV) co-infected, respectively] treated with efavirenz 600 mg once a day in combination with other antiretroviral agents, plasma concentration was measured at least 8 h after the last drug intake using a validated HPLC method. The degree of liver fibrosis was determined by means of either liver biopsy or non-invasive biochemical markers (Fibrotest®). The proportions of patients above a threshold of 4000 ng/mL were compared by means of Pearson’s {chi}2 test or Fisher's exact test.

Results: In HIV mono-infected and HIV/HCV and HIV/HBV co-infected patients, mean ± SD efavirenz plasma concentrations were 3060 ± 1928, 4108 ± 3324 and 3163 ± 2432 ng/mL, respectively. The proportion of patients with an efavirenz concentration above 4000 ng/mL differed significantly according to the presence of hepatitis and the fibrosis stage. A concentration above 4000 ng/mL was found in 14 patients (18.2%) mono-infected with HIV compared with 5 (22.7%, P = 0.01) and 9 (25.7%, P = 0.001) HIV/HBV or HIV/HCV co-infected patients, respectively. When the fibrosis stage was considered in all patients with hepatitis, 3 cirrhotic patients (42.6%) had an efavirenz concentration above the 4000 ng/mL threshold [compared with 14 (18.2%) HIV mono-infected patients, P = 0.001].

Conclusions: Therapeutic drug monitoring may be of interest in cirrhotic patients more at risk of side effects due to efavirenz overdosing.

Keywords: antiretrovirals , drug monitoring , tolerance


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