Publications & Reports

Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.

Applegate TL, Gaudieri S, Plauzolles A, Chopra A, Grebely J, Lucas M, Hellard M, Luciani F, Dore GJ, Matthews GV
The Kirby Institute, UNSW Australia, Sydney, Australia. tapplegate@kirby.unsw.edu.au.

Abstract

BACKGROUND: Directly Acting Antivirals (DAAs) are predicted to transform hepatitis C (HCV) therapy, yet little is known about the prevalence of naturally occurring resistance mutations in recently acquired HCV. This study aimed to determine the prevalence and frequency of drug resistance mutations in the viral quasispecies among HIV positive and negative individuals with recent HCV. METHODS: The NS3 protease, NS5A and NS5B polymerase genes were amplified from fifty genotype 1a participants of the Australian Trial in Acute Hepatitis C. Amino acid variations at sites known to be associated with possible drug resistance were analysed by ultra-deep pyrosequencing. RESULTS: Twelve percent of individuals harboured dominant resistance mutations, while 36% demonstrated non dominant resistant variants below that detectable by bulk sequencing (ie < 20%) but above a threshold of 1%. Resistance variants (< 1%) were observed at most sites associated with DAA resistance from all classes, with the exception of sofosbuvir. CONCLUSIONS: Dominant resistant mutations were uncommonly observed in the setting of recent HCV. However, low level mutations to all DAA classes were observed by deep sequencing at the majority of sites, and in most individuals. The significance of these variants and impact on future treatment options remains to be determined.

Full text of this article is available at link on the right hand side of this page. This is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including peer review, editing and formatting, might not be reflected in this document. A definitive version will be published in Antiviral Therapy, International Medical Press. See http://www.intmedpress.com/serveFile.cfm?sUID=cbdb11e7-04ee-4d5b-9eaf-fb360c2a38d1

Publication

  • Journal: Antiviral Therapy
  • Published: 01/01/2015
  • Volume: 20
  • Issue: 2
  • Pagination: 199-208

Author

Health Issue

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