Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alpha-2a plus ribavirin

Aliment Pharmacol Ther. 2008 Jul;28(1):43-50. doi: 10.1111/j.1365-2036.2008.03705.x. Epub 2008 Apr 7.


Background: The impact of reduced drug exposure on outcomes in patients with chronic hepatitis C has not been determined in routine clinical practice.

Aim: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Recombinant Proteins
  • Ribavirin / administration & dosage*
  • Treatment Outcome


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a