title: Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections.
abstract: OBJECTIVE
  We evaluated antiviral activity of 2 weeks therapy with telaprevir alone, peginterferon alfa-2a and ribavirin (PR), or all 3 drugs (TPR) in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections.
  
  
  METHODS
  We performed a randomized, multicenter, partially blinded study of patients (23 with HCV genotype 2, 26 with genotype 3) who received telaprevir (750 mg every 8 h), placebo plus PR (peginterferon, 180 μg, once weekly and ribavirin, 400 mg, twice daily), or TPR for 15 days, followed by PR for 22 or 24 weeks. Plasma levels of HCV RNA were quantified.
  
  
  RESULTS
  Levels of HCV RNA decreased in all patients with HCV genotype 2, including those who received telaprevir monotherapy. The decrease was more rapid among patients who received telaprevir. By day 15, 0% (telaprevir), 40% (TPR), and 22% (PR) of patients with HCV genotype 2 had undetectable levels of HCV RNA; rates of sustained virologic response were 56%, 100%, and 89%, respectively. Overall, 6 of 9 HCV genotype 2 patients that received only telaprevir had viral breakthrough within 15 days after an initial response. HCV RNA levels decreased slightly among patients with HCV genotype 3 who received telaprevir and decreased rapidly among patients given PR or TPR (telaprevir had no synergistic effects with PR). Sustained virologic response rates were 50%, 67%, and 44% among patients given telaprevir, TPR, or PR respectively; 7 patients with HCV genotype 3 relapsed after therapy (2 given telaprevir, 3 given TPR, and 2 given PR) and 3 patients with HCV genotype 3 had viral breakthrough during telaprevir monotherapy. The incidence of adverse events was similar among groups.
  
  
  CONCLUSIONS
  Telaprevir monotherapy for 2 weeks reduces levels of HCV RNA in patients with chronic HCV genotype 2 infections, but has limited activity in patients with HCV genotype 3.
authors.affiliation: Queen Marys University of London, Blizard Institute of Cellular and Molecular Science, London, UK. g.r.foster@qmul.ac.uk
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Verlinden
authors.forename: Rolf
authors.initials: R
authors.lastname: van Heeswijk
authors.forename: Ben
authors.initials: B
authors.lastname: van Baelen
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a