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Antivir Ther. 2018;23(4):307-314. doi: 10.3851/IMP3184.

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

Author information

1
Laboratoire Alphabio, Marseille, France.
2
Hôpital Européen, Marseille, France.
3
CHU Lyon, Lyon, France.
4
CHU Toulouse Purpan, Toulouse, France.
5
CHU Grenoble Alpes, Grenoble, France.
6
CHU Bordeaux, Bordeaux, France.
7
CHU Toulouse Purpan, UMR 152 IRD Toulouse 3, Toulouse, France.
8
Hôpital Michallon, Grenoble, France.
9
Institut Arnault Tzanck, Saint-Laurent-du-Var, France.
10
Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France.
11
Hôpital Saint-Joseph, Marseille, France.

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.

PMID:
28730994
DOI:
10.3851/IMP3184
[Indexed for MEDLINE]

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