title: Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment.
abstract: OBJECTIVE
  To maximize sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, treatment with pegylated interferon and ribavirin has been genotype-specific (1 vs non-1). We evaluated the effects of ribavirin and peginterferon alfa-2a dose reductions on SVR in patients infected with HCV genotype 1.
  
  
  METHODS
  Data were pooled from 569 patients enrolled in 2 phase III trials of 48 weeks of treatment with peginterferon alfa-2a and ribavirin. All patients were evaluated for the effect of cumulative drug exposure on 4- and 12-week responses, and the 427 patients who completed treatment were evaluated for effect of drug exposure on SVR.
  
  
  RESULTS
  Of patients who completed treatment, more had reductions (< or =97% cumulative dose) of ribavirin than of peginterferon alfa-2a (43% vs 27%). Neither early virologic response nor SVR was affected adversely by ribavirin reductions when the cumulative ribavirin exposure was greater than 60%. The SVR was reduced significantly (P = .0006) in patients with less than the 60% cumulative ribavirin dose and was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had minimal impact on SVR in patients who achieved rapid virologic response, defined as undetectable HCV RNA levels after 4 weeks, even when they received less than the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virologic response.
  
  
  CONCLUSIONS
  Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR.
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA. rajender.reddy@uphs.upenn.edu
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Stephanos
authors.initials: S
authors.lastname: Hadziyannis
authors.forename: Fayez M
authors.initials: FM
authors.lastname: Hamzeh
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wright
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a