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Original article

The impact of ribavirin plasma concentration on the efficacy of the interferon-sparing regimen, sofosbuvir and ribavirin

Marianne Martinello, Ana Schteinman, Maryam Alavi, Kenneth Williams, Gregory J Dore, Richard Day, Gail V Matthews

Corresponding author name: Marianne Martinello
Corresponding author e-mail: mmartinello@kirby.unsw.edu.au

Citation: Antiviral Therapy 2016; 21:127-132
doi: 10.3851/IMP2984

Date accepted: 16 August 2015
Date published online: 24 August 2015

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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