Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

PLoS One. 2016 May 11;11(5):e0155142. doi: 10.1371/journal.pone.0155142. eCollection 2016.

Abstract

In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes.

Trial registration: ClinicalTrials.gov NCT01226771.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / metabolism
  • Anemia / complications*
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Hemoglobins / metabolism
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • RNA, Viral / metabolism
  • Ribavirin / administration & dosage
  • Ribavirin / blood
  • Ribavirin / pharmacokinetics*
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

  • Chemokine CXCL10
  • Hemoglobins
  • RNA, Viral
  • Ribavirin
  • Alanine Transaminase

Associated data

  • ClinicalTrials.gov/NCT01226771

Grants and funding

This work was supported by the Swedish Medical Research Council (Vetenskapsrådet; Diarienr 2008:2427 and 2011:3821), and ALF Funds at the Sahlgrenska University Hospital (Diarienr ALFGBG-143271). An unrestricted grant from Roche affiliates in the Nordic region also supported this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.