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
Artikel i vetenskaplig tidskrift, 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.
Författare
Jesper Waldenström
Göteborgs universitet
Johan Westin
Göteborgs universitet
Kristina Nyström
Göteborgs universitet
Peer B Christensen
Syddansk Universitet
O. Dalgard
Akershus University Hospital
Martti Färkkilä
Helsingin Yliopisto
K. Lindahl
Karolinska universitetssjukhuset
Staffan Nilsson
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Matematisk statistik
Gunnar Norkrans
Göteborgs universitet
H. Krarup
Aalborg Sygehus
H. Norrgren
Skånes universitetssjukhus (SUS)
Mads Rauning Buhl
Aarhus Universitet
S. Stenmark
Martin Lagging
Göteborgs universitet
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 11 5 e0155142- e0155142Ämneskategorier
Infektionsmedicin
DOI
10.1371/journal.pone.0155142