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1 April 2007

Volume 195, Number 7
The Journal of Infectious Diseases 2007;195:973–979
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19507-0010$15.00
DOI: 10.1086/512086
MAJOR ARTICLE

Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV‐Infected Patients with Chronic Hepatitis C

Pablo Barreiro,1

Sonia Rodríguez‐Novoa,2

Pablo Labarga,1

Andrés Ruiz,1

Inmaculada Jiménez‐Nácher,2

Luz Martín‐Carbonero,1

Juan Gonzalez‐Lahoz,1 and

Vincent Soriano1

1Department of Infectious Diseases and 2Pharmacokinetic Unit, Hospital Carlos III, Madrid, Spain

Background.Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency.

Methods.Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)–coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry.

Results.A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; ) and NVP (median, 6.6 vs. 5.8 μg/mL; ). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; ). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; ). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis.

Conclusions.Liver clearance of nonnucleoside reverse‐transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV‐coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.

Received 20 August 2006; accepted 20 October 2006; electronically published 20 February 2007.

Reprints or correspondence: Dr. Vincent Soriano, Dept. of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, 28029 Madrid, Spain ().

Cited by

J.-L. Meynard, K. Lacombe, J.-M. Poirier, J. Legrand, L. Morand-Joubert, P.-M. Girard. (2009) Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or C. Journal of Antimicrobial Chemotherapy 63:3, 579-584
Online publication date: 15-Feb-2009.
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Kentaro Yoshioka, Naoto Kawabe, Senju Hashimoto. (2008) Transient elastography: Applications and limitations. Hepatology Research 38:11, 1063-1068
Online publication date: 1-Dec-2008.
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Sofia A. Pereira, Umbelina Caixas, Teresa Branco, Isabel Germano, Fátima Lampreia, Ana L. Papoila, Emília C. Monteiro. (2008) Efavirenz concentrations in HIV-infected patients with and without viral hepatitis. British Journal of Clinical Pharmacology 66:4, 551-555
Online publication date: 1-Nov-2008.
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Vincent Soriano, Massimo Puoti, Marion Peters, Yves Benhamou, Mark Sulkowski, Fabien Zoulim, Stefan Mauss, Juergen Rockstroh. (2008) Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS 22:12, 1399-1410
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Online publication date: 1-Jul-2008.
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Mauro S Torno, Mallory D Witt, Akihiko Saitoh, Courtney V Fletcher. (2008) Successful Use of Reduced-Dose Efavirenz in a Patient with Human Immunodeficiency Virus Infection: Case Report and Review of the Literature. Pharmacotherapy 28:6, 782-787
Online publication date: 1-Jul-2008.
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Matthijs van Luin, Paul FM Kuks, David M Burger. (2008) Use of therapeutic drug monitoring in HIV disease. Current Opinion in HIV and AIDS 3:3, 266-271
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Emma C. Thomson, Janice Main. (2008) Epidemiology of hepatitis C virus infection in HIV-infected individuals. Journal of Viral Hepatitis 0:0, 080423192604581-???
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Vincent Soriano, Massimo Puoti, Pilar Garcia-Gascó, Juergen K Rockstroh, Yves Benhamou, Pablo Barreiro, Barbara McGovern. (2008) Antiretroviral drugs and liver injury. AIDS 22:1, 1-13
Online publication date: 1-Feb-2008.
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Curtis L Cooper. (2007) HIV antiretroviral medications and hepatotoxicity. Current Opinion in HIV and AIDS 2:6, 466-473
Online publication date: 1-Dec-2007.
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C. Castellares, P. Barreiro, L. Martín-Carbonero, P. Labarga, M. E. Vispo, R. Casado, L. Galindo, P. García-Gascó, J. García-Samaniego, V. Soriano. (2007) Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. Journal of Viral Hepatitis 0:0, 070827235139002-???
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  • Potential conflicts of interest: none reported.

    Financial support: Fundación Investigación y Educación en SIDA; Red de Investigación en SIDA; European Surveillance Network for Vigilance against Viral Resistance; Instituto de Salud Carlos III; Fondo de Investigaciones Sanitarias; Agencia Lain Entralgo.

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