title: Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV.
abstract: Resistance-associated variants (RAVs) represent a challenge to the success of new HCV therapies. The aim of this study was to describe the prevalence of naturally occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-naïve patients infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and sample collection were performed between 2011 and 2013. Using Sanger-based sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3 %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V (3.2-6.3 %). Understanding the real RAVs scenario in patients is fundamental to establishing the most effective therapeutic strategy and in minimizing the risks for their selection.
authors.affiliation: Laboratory of Tropical Gastroenterology and Hepatology "João Alves de Queiroz and Castorina Bittencourt Alves", LIM-07, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, 05403-000, Brazil.|Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Caroline Furtado
authors.initials: CF
authors.lastname: Noble
authors.affiliation: Laboratory of Tropical Gastroenterology and Hepatology "João Alves de Queiroz and Castorina Bittencourt Alves", LIM-07, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, 05403-000, Brazil. femalta@yahoo.com.|Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. femalta@yahoo.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Malta
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Lisboa-Neto
authors.affiliation: Laboratory of Tropical Gastroenterology and Hepatology "João Alves de Queiroz and Castorina Bittencourt Alves", LIM-07, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, 05403-000, Brazil.|Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Michele Soares
authors.initials: MS
authors.lastname: Gomes-Gouvêa
authors.affiliation: Health Center, Caxias do Sul, RS, Brazil.
authors.forename: Andrea Gurgel Batista
authors.initials: AGB
authors.lastname: Leite
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Vanessa Fusco Duarte
authors.initials: VFD
authors.lastname: de Castro
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Rubia Anita Ferraz
authors.initials: RAF
authors.lastname: Santana
authors.affiliation: Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.|Laboratory of Virology, LIM-52, Institute of Tropical Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Cássia
authors.initials: MC
authors.lastname: Mendes-Correa
authors.affiliation: Laboratory of Tropical Gastroenterology and Hepatology "João Alves de Queiroz and Castorina Bittencourt Alves", LIM-07, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, 05403-000, Brazil.|Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.|Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: João Renato Rebello
authors.initials: JRR
authors.lastname: Pinho
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001938:Brazil; D024882:Drug Resistance, Viral; D005787:Gene Frequency; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase