title: Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin.
abstract: The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24-72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
authors.affiliation: Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden. magnus.lindh@microbio.gu.se
authors.forename: M
authors.initials: M
authors.lastname: Lindh
authors.forename: B
authors.initials: B
authors.lastname: Arnholm
authors.forename: P
authors.initials: P
authors.lastname: Björkman
authors.forename: K
authors.initials: K
authors.lastname: Hellstrand
authors.forename: M
authors.initials: M
authors.lastname: Lagging
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: T
authors.initials: T
authors.lastname: Wahlberg
authors.forename: E
authors.initials: E
authors.lastname: Wallmark
authors.forename: O
authors.initials: O
authors.lastname: Weiland
authors.forename: R
authors.initials: R
authors.lastname: Wejstål
authors.forename: J
authors.initials: J
authors.lastname: Westin
authors.forename: A
authors.initials: A
authors.lastname: Widell
authors.forename: G
authors.initials: G
authors.lastname: Norkrans
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a