Interferon and ribavirin therapy does not select for resistance mutations in hepatitis C virus polymerase.

Journal Article

Ribavirin has a minor and transient effect on hepatitis C virus (HCV) replication and has been suggested to select a novel mutation, F415Y, in the RNA-dependent RNA polymerase of subtype 1a viruses. Twenty-nine patients with chronic hepatitis C (subtyped by INNO LiPA as 1a, 17; 1b, 11; 1a/1b, 1) who were nonresponders to interferon-based therapies were identified retrospectively and screened at Baseline, week 24 of treatment, and 24 weeks post-treatment. Selection of resistance mutations, including at amino acid position 415 of the polymerase, was investigated. Using clonal sequencing and pyrosequencing of the NS5B gene, we screened for the F415Y resistance mutation among patients who received combination therapy with ribavirin and interferon α. Of the 15 subtype 1a patients treated with interferon plus ribavirin, only one had the F415Y change at week 24, and an F/Y mixture was still present 24 weeks after therapy. Four additional patients in this group had the F415Y change 24 weeks post-therapy. The NS5B genes were sequenced in order to identify amino acid changes associated with ribavirin therapy, but no evidence was found that ribavirin selects for particular amino acids in the RNA-dependent RNA polymerase. Ribavirin, a weak inhibitor of HCV replication, does not select for resistance mutations in the sequence of the HCV RNA polymerase.

Full Text

Duke Authors

Cited Authors

  • Ward, CL; Dev, A; Rigby, S; Symonds, WT; Patel, K; Zekry, A; Pawlotsky, J-M; McHutchison, JG

Published Date

  • August 2008

Published In

Volume / Issue

  • 15 / 8

Start / End Page

  • 571 - 577

PubMed ID

  • 18363671

Pubmed Central ID

  • 18363671

Electronic International Standard Serial Number (EISSN)

  • 1365-2893

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2893.2008.00980.x

Language

  • eng

Conference Location

  • England