Baseline hepatitis C virus resistance-associated substitutions present at frequencies lower than 15% may be clinically significant

Celia Perales, Qian Chen, Maria Eugenia Soria, Josep Gregori, Damir Garcia-Cehic, Leonardo Nieto-Aponte, Lluis Castells, Arkaitz Imaz, Meritxell Llorens-Revull, Esteban Domingo, Maria Buti, Juan Ignacio Esteban, Francisco Rodriguez-Frias, Josep Quer

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15 Citations (Scopus)

Abstract

© 2018 Perales et al. Background: Controversy is ongoing about whether a minority mutant present at frequencies below 15% may be clinically relevant and should be considered to guide treatment. Methods: Resistance-associated substitution (RAS) studies were performed in patients before and at failure of antiviral treatments using Next-generation hepatitis C virus (HCV) sequencing (NGS). Results: We have found two patients with genotype 1a infection having RAS in 3.5%–7.1% of the viral population at baseline that were selected during ledipasvir + sofosbuvir treatment. Co-selection of RAS located in a region not directly affected by the antiviral treatment also occurred. This observation calls into question, the recommendations to guide RAS-based direct-acting antiviral (DAA) treatment only when RAS are present in >15% of the sequences generated. Conclusion: Our results suggests that RAS study should include all three HCV DAA target proteins and minority mutants should be considered as clinically relevant.
Original languageEnglish
Pages (from-to)2207-2210
JournalInfection and Drug Resistance
Volume11
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Antiviral resistance
  • HCV
  • Minority mutants
  • NGS

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