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
Journal article, 2016
In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. 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-alpha 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 antiviral effect differently regulated across IL28B genotypes.
Author
Jesper Waldenström
University of Gothenburg
Johan Westin
University of Gothenburg
Kristina Nyström
University of Gothenburg
Peer B Christensen
University of Southern Denmark
O. Dalgard
Akershus University Hospital
Martti Färkkilä
University of Helsinki
K. Lindahl
Karolinska University Hospital
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
Gunnar Norkrans
University of Gothenburg
H. Krarup
Aalborg Sygehus
H. Norrgren
Skåne University Hospital
Mads Rauning Buhl
Aarhus University
S. Stenmark
Martin Lagging
University of Gothenburg
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 11 5 e0155142- e0155142Subject Categories
Infectious Medicine
DOI
10.1371/journal.pone.0155142