title: Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV/hepatitis C virus-coinfected patients.
abstract: OBJECTIVE
  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 log10 IU/mL (range 2-3 log10 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.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: D L
authors.initials: DL
authors.lastname: Braun
authors.forename: A
authors.initials: A
authors.lastname: Rauch
authors.forename: N
authors.initials: N
authors.lastname: Durisch
authors.forename: N
authors.initials: N
authors.lastname: Eberhard
authors.forename: A
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: B
authors.initials: B
authors.lastname: Ledergerber
authors.forename: K J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: J
authors.initials: J
authors.lastname: Böni
authors.forename: R
authors.initials: R
authors.lastname: Weber
authors.forename: J
authors.initials: J
authors.lastname: Fehr
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011480:Protease Inhibitors / Q000008:administration & dosage; D012367:RNA, Viral / Q000032:analysis; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D012838:Silymarin; D000077385:Silybin
keywords: HIV/hepatitis C virus coinfection; advanced liver fibrosis; hepatitis C virus; nonresponse; null response; silibinin