title: Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection.
abstract: In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
authors.affiliation: Department of Infectious Diseases, University of Southern Denmark, Odense C, Denmark. court.pedersen@ouh.regionsyddanmark.dk
authors.forename: C
authors.initials: C
authors.lastname: Pedersen
authors.forename: Å
authors.initials: Å
authors.lastname: Alsiö
authors.forename: M
authors.initials: M
authors.lastname: Lagging
authors.forename: N
authors.initials: N
authors.lastname: Langeland
authors.forename: M
authors.initials: M
authors.lastname: Färkkilä
authors.forename: M Rauning
authors.initials: MR
authors.lastname: Buhl
authors.forename: K
authors.initials: K
authors.lastname: Mørch
authors.forename: J
authors.initials: J
authors.lastname: Westin
authors.forename: P
authors.initials: P
authors.lastname: Sangfelt
authors.forename: G
authors.initials: G
authors.lastname: Norkrans
authors.forename: P Brehm
authors.initials: PB
authors.lastname: Christensen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a