title: No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy.
abstract: Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Luísa
authors.initials: L
authors.lastname: Hoffmann
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Débora Souza
authors.initials: DS
authors.lastname: Faffe
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Jennifer Fróes Cruz
authors.initials: JF
authors.lastname: Lima
authors.affiliation: Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
authors.forename: Thayanna Araujo
authors.initials: TA
authors.lastname: Capitanio
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Bianca Catarina Azeredo
authors.initials: BC
authors.lastname: Cabral
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Turán Péter
authors.initials: TP
authors.lastname: Ürményi
authors.affiliation: Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
authors.forename: Henrique Sergio Moraes
authors.initials: HS
authors.lastname: Coelho
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Rondinelli
authors.affiliation: Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
authors.forename: Cristiane Alves
authors.initials: CA
authors.lastname: Villela-Nogueira
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Rosane
authors.initials: R
authors.lastname: Silva
keywords: Drug resistance; Genetic diversity; HCV; NGS; NS3 protease; Telaprevir