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Efficacy of lead‐in silibinin and subsequent triple therapy in difficult‐to‐treat HIV /hepatitis C virus‐coinfected patients
Author(s) -
Braun DL,
Rauch A,
Durisch N,
Eberhard N,
Anagnostopoulos A,
Ledergerber B,
Metzner KJ,
Böni J,
Weber R,
Fehr J
Publication year - 2014
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12166
Subject(s) - silibinin , medicine , ribavirin , hepatitis c virus , hepatitis c , telaprevir , combination therapy , gastroenterology , coinfection , immunology , pharmacology , virus
Objectives The efficacy of current hepatitis C virus ( HCV ) triple therapy, including a protease inhibitor, is limited in HIV / HCV ‐coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon‐ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response ( SVR ) during triple therapy and cannot wait for next‐generation anti‐ HCV drugs. In a pilot study, we investigated the efficacy of a lead‐in therapy with silibinin before triple therapy in difficult‐to‐treat patients. Methods Inclusion criteria were HIV / HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon‐ribavirin treatment. Intervention was lead‐in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon‐ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon‐ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead‐in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment. Results We examined six HIV / HCV ‐coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log 10 IU /mL (range 2–3 log 10 IU /mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24. Conclusions A lead‐in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult‐to‐treat HIV / HCV ‐coinfected patients with advanced liver fibrosis and previous failure of peginterferon‐ribavirin.