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. 2018 Nov 8:11:2207-2210.
doi: 10.2147/IDR.S172226. eCollection 2018.

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

Celia Perales  1   2 , Qian Chen  1   2 , Maria Eugenia Soria  1 , Josep Gregori  1   2   3 , Damir Garcia-Cehic  1   2 , Leonardo Nieto-Aponte  4 , Lluis Castells  1   2 , Arkaitz Imaz  5 , Meritxell Llorens-Revull  1 , Esteban Domingo  2   6 , Maria Buti  1   2   7 , Juan Ignacio Esteban  1   2   7 , Francisco Rodriguez-Frias  2   4   7 , Josep Quer  1   2   7
Affiliations

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

Celia Perales et al. Infect Drug Resist. .

Abstract

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.

Keywords: HCV; NGS; antiviral resistance; minority mutants.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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