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Original article

Baseline and post-treatment hepatitis C NS5A resistance in relapsed patients from a multicentric real-life cohort

Philippe Halfon, Caroline Scholtès, Jacques Izopet, Sylvie Larrat, Pascale Trimoulet, Fabien Zoulim, Laurent Alric, Sophie Métivier, Vincent Leroy, Denis Ouzan, Victor de Lédinghen, Sofiane Mohamed, Guillaume Pénaranda, Hacène Khiri, Marie-Ange Thélu, Anne Plauzolles, Laurent Chiche, Marc Bourlière, Florence Abravanel

Corresponding author name: Philippe Halfon
Corresponding author e-mail: philippe.halfon@alphabio.fr

Citation: Antiviral Therapy 2018; 23:307-314
doi: 10.3851/IMP3184

Date accepted: 14 July 2017
Date published online: 21 July 2017

Abstract

Background: Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors.

Methods: From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients.

Results: Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance).

Conclusions: This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment.

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