Progression of Fibrosis in HIV and Hepatitis C Virus–Coinfected Patients Treated with Interferon plus Ribavirin‐Based Therapy: Analysis of Risk Factors
1Groupe Hospitalier Universitaire Est, Université Paris 6, INSERM U707, 2Groupe Hospitalier Universitaire Nord, Université Paris 7, 3Groupe Hospitalier Universitaire Ouest, Université Paris 5, INSERM U370, and 4Groupe Hospitalier Universitaire Est, UMR 7087, Université Pierre et Marie Curie, Paris‐6, Paris, 5Hopital Gui de Chauliac, Montpellier, 6Centre Hospitalier Universitaire Raymond Poincaré, Université de Versailles, Garches, and 7Laboratoire Alphabio‐CDL Pharma et Hôpital Ambroise Paré, Marseille, France
Background.
We determined the prevalence and determinants of worsening fibrosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving anti‐HCV therapy.
Methods.Among 383 HIV‐HCV–coinfected patients who received at least 1 dose of anti‐HCV treatment (weekly subcutaneous injections of 1.5 μg/kg pegylated interferon‐α‐2b plus daily ribavirin or thrice‐weekly subcutaneous injections of 3 MU of interferon‐α‐2b plus daily ribavirin for 48 weeks), paired pretreatment and posttreatment liver biopsy specimens were available and interpretable for 198 cases. Hepatic necroinflammation and fibrosis were graded with Ishak’s classification. Histological worsening of fibrosis was defined as a score increase of 
2 points in patients with fibrosis stage of <4 and as a score increase of 1 point in patients with stage‐5 fibrosis.
Results.The mean 
deviation between the 2 biopsies was 
weeks. Fibrosis worsened in 34 patients (17.1%). In univariate analysis, ongoing antiretroviral therapy, failure to achieve a sustained viral response, nucleoside reverse‐transcriptase inhibitor therapy, didanosine therapy, and stavudine therapy were significantly associated with worsening of fibrosis. Didanosine (odds ratio, 3.34; 95% confidence interval, 1.39–7.96; 
) and failure to have a sustained viral response (odds ratio, 9.05; 95% confidence interval, 2.06–39.66; 
) remained significantly associated with worsening of fibrosis.
Conclusion.The mitochondrial toxicity of antiretrovirals, such as didanosine, seems to play a major role in worsening of fibrosis during HCV therapy. Therefore, anti‐HCV therapy should ideally be administered before antiretroviral treatment initiation. If anti‐HCV and anti‐HIV treatments have to be administered concomitantly, then nucleoside reverse‐transcriptase inhibitors with the lowest mitochondrial toxicity should be preferred.
Received 23 July 2007; accepted 5 November 2007; electronically published 6 February 2008.
Cited by
Online publication date: 1-Jun-2009.
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Online publication date: 1-Feb-2009.
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