title: 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.
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.
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Waldenström
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Nyström
authors.affiliation: Department of Infectious Diseases, University of Southern Denmark, Odense, Denmark.
authors.forename: Peer
authors.initials: P
authors.lastname: Christensen
authors.affiliation: Department of Infectious Diseases, Akershus University Hospital, Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Dalgard
authors.affiliation: Department of Gastroenterology, Helsinki University, Helsinki, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Lindahl
authors.affiliation: Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norkrans
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Krarup
authors.affiliation: Department of Infectious Diseases, Skåne University Hospital, Lund, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Norrgren
authors.affiliation: Department of Infectious Diseases, Aarhus University, Aarhus, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Rauning Buhl
authors.affiliation: Department of Communicable Disease Control Västerbotten, Umeå, Sweden.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stenmark
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D000740:Anemia / Q000150:complications*; D054357:Chemokine CXCL10 / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000378:metabolism; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D054357:Chemokine CXCL10; D006454:Hemoglobins; D012367:RNA, Viral; D012254:Ribavirin; D000410:Alanine Transaminase