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Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy

Author

Listed:
  • Julia Dietz
  • Daniel Rupp
  • Simone Susser
  • Johannes Vermehren
  • Kai-Henrik Peiffer
  • Natalie Filmann
  • Dimitra Bon
  • Thomas Kuntzen
  • Stefan Mauss
  • Georgios Grammatikos
  • Dany Perner
  • Caterina Berkowski
  • Eva Herrmann
  • Stefan Zeuzem
  • Ralf Bartenschlager
  • Christoph Sarrazin

Abstract

Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P

Suggested Citation

  • Julia Dietz & Daniel Rupp & Simone Susser & Johannes Vermehren & Kai-Henrik Peiffer & Natalie Filmann & Dimitra Bon & Thomas Kuntzen & Stefan Mauss & Georgios Grammatikos & Dany Perner & Caterina Berk, 2016. "Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-17, June.
    • Handle: RePEc:plo:pone00:0156731
    DOI: 10.1371/journal.pone.0156731
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