title: The impact of ribavirin plasma concentration on the efficacy of the interferon-sparing regimen, sofosbuvir and ribavirin.
abstract: Ribavirin augments sustained virological response when administered with pegylated interferon for the treatment of chronic HCV infection. The impact of ribavirin plasma concentration on outcome in individuals receiving interferon-free regimens has not been evaluated.
  
  
  
  Stored plasma samples were retrieved for 47 treatment-naive subjects who received sofosbuvir and weight-based ribavirin for 12-24 weeks in the Phase IIb QUANTUM study. Week 1, 4 and 8 ribavirin plasma concentrations (mg/l) were quantified using high-performance liquid chromatography with UV detection.
  
  
  
  Sustained virological response at 12 weeks post treatment was observed in 55% with all treatment failures due to relapse. The median ribavirin plasma concentration increased from week 1 (1.58 mg/l, IQR 1.44-2.24) to week 4 (2.23 mg/l, IQR 1.69-2.87) and week 8 (2.67 mg/l, IQR 2.10-3.26) with wide variability at steady state. Median week 4 ribavirin plasma concentration was 2.25 mg/l (IQR 1.63-3.05) in those with a sustained virological response as compared to 2.07 mg/l (IQR 1.79-2.86) in those with treatment failure (OR 1.35; 95% CI 0.76, 2.39; P=0.3). No significant association between ribavirin plasma concentration and treatment response was noted at weeks 1 or 8.
  
  
  
  We found no evidence of an association between ribavirin plasma concentrations and relapse suggesting that, as opposed to interferon-based therapy, suboptimal ribavirin plasma concentrations did not explain the high rate of virological failure with this regimen. Our findings suggest that in interferon-free ribavirin-containing regimens, concerns over ribavirin dosing to achieve previously determined target plasma concentrations are unnecessary.
authors: Kirby Institute, UNSW, Sydney, Australia. mmartinello@kirby.unsw.edu.au.
authors: Marianne
authors: M
authors: Martinello
authors: Ana
authors: A
authors: Schteinman
authors: Maryam
authors: M
authors: Alavi
authors: Kenneth
authors: K
authors: Williams
authors: Gregory J
authors: GJ
authors: Dore
authors: Richard
authors: R
authors: Day
authors: Gail V
authors: GV
authors: Matthews
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D054314:Drug Inverse Agonism; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069474:Sofosbuvir / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir