title: Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alpha-2a plus ribavirin.
abstract: BACKGROUND
  The impact of reduced drug exposure on outcomes in patients with chronic hepatitis C has not been determined in routine clinical practice.
  
  
  OBJECTIVE
  To examine the impact of exposure to peginterferon alpha-2a and ribavirin on early virological response (EVR) and sustained virological response (SVR) in treatment-naive patients with HCV genotype 1 infection enrolled in a large expanded access programme.
  
  
  METHODS
  Eight hundred and ninety-one patients treated for 48 weeks with an initial ribavirin dose of 800 or 1000/1200 mg/day were evaluated. Ribavirin 1000 mg/day (<75 kg) or 1200 mg/day (>or=75 kg) and peginterferon alpha-2a 180 microg/week were considered optimal. The impact of reduced drug exposure (expressed as a percentage of optimal) on EVR and SVR was evaluated.
  
  
  RESULTS
  Mean ribavirin exposure in week 0-12 was 70% and 96% in patients assigned to ribavirin 800 and 1000/1200 mg/day, respectively. EVR and SVR rates were lower in patients assigned to ribavirin 800 than 1000/1200 mg/day (EVR, 75% vs. 84%, respectively, P < 0.001; SVR, 45% vs. 54%, respectively, P = 0.011). Furthermore, there was a strong correlation between achievement of EVR and SVR and ribavirin dose over the first 12 weeks expressed either as absolute dose or proportion of optimal dose received (P < 0.001 for both).
  
  
  CONCLUSIONS
  Ribavirin exposure to week 12 is significantly associated with EVR and SVR in genotype 1 patients. Maintenance of an optimal ribavirin dose is the most important modifiable factor during combination therapy for chronic hepatitis C.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, Canada. vince.bain@ualberta.ca
authors.forename: V G
authors.initials: VG
authors.lastname: Bain
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Peltekian
authors.forename: E M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Deschênes
authors.forename: M
authors.initials: M
authors.lastname: Sherman
authors.forename: R
authors.initials: R
authors.lastname: Bailey
authors.forename: H
authors.initials: H
authors.lastname: Witt-Sullivan
authors.forename: R
authors.initials: R
authors.lastname: Balshaw
authors.forename: M
authors.initials: M
authors.lastname: Krajden
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a