Baseline and Post-Treatment Hepatitis C NS5A Resistance in Relapsed Patients from a Multicentric Real-Life Cohort. Issue 4 (May 2018)

• Record Type: Journal Article
• Authors: Halfon, Philippe; Scholtès, Caroline; Izopet, Jacques; Larrat, Sylvie; Trimoulet, Pascale; Zoulim, Fabien; Alric, Laurent; Métivier, Sophie; Leroy, Vincent; Ouzan, Denis; De Lédinghen, Victor; Mohamed, Sofane; Pénaranda, Guillaume; Khiri, Hacène; Thélu, Marie-Ange; Plauzolles, Anne; Chiche, Laurent; Bourlière, Marc; Abravanel, Florence
• Is Part Of: Antiviral therapy. Volume 23:Issue 4(2018)
• Page Start: 307
• Page End: 314
• Publication Date: 2018-05
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3184
• Languages: English
• ISSNs: 1359-6535

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.