title: Naturally occurring NS3 resistance-associated variants in hepatitis C virus genotype 1: Their relevance for developing countries.
abstract: Hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with an estimated 130-150 million infected individuals worldwide. HCV is a leading cause of chronic liver diseases including cirrhosis and hepatocellular carcinoma. Current treatment options in developing countries involve pegylated interferon-α and ribavirin as dual therapy or in combination with one or more direct-acting antiviral agents (DAA). The emergence of resistance-associated variants (RAVs) after treatment reveals the great variability of this virus leading to a great difficulty in developing effective antiviral strategies. Baseline RAVs detected in DAA treatment-naïve HCV-infected patients could be of great importance for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS3 protease inhibitor mutations has been addressed in many countries, there are only a few reports on their prevalence in South America. In this study, we investigated the presence of RAVs in the HCV NS3 serine protease region by analysing a cohort of Uruguayan patients with chronic hepatitis C who had not been treated with any DAAs and compare them with the results found for other South American countries. The results of these studies revealed that naturally occurring mutations conferring resistance to NS3 inhibitors exist in a substantial proportion of Uruguayan treatment-naïve patients infected with HCV genotype 1 enrolled in these studies. The identification of these baseline RAVs could be of great importance for patients' management and outcome prediction in developing countries.
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Natalia
authors.initials: N
authors.lastname: Echeverría
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Betancour
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Gámbaro
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, 11600 Montevideo, Uruguay.
authors.forename: Nelia
authors.initials: N
authors.lastname: Hernández
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, 11600 Montevideo, Uruguay.
authors.forename: Pablo
authors.initials: P
authors.lastname: López
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, 11600 Montevideo, Uruguay.
authors.forename: Daniela
authors.initials: D
authors.lastname: Chiodi
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, 11600 Montevideo, Uruguay.
authors.forename: Adriana
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Laboratorio de Biología Molecular, Asociación Española, Palmar 1465, Montevideo, Uruguay, Uruguay.
authors.forename: Susana
authors.initials: S
authors.lastname: Boschi
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Fajardo
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Martín
authors.initials: M
authors.lastname: Sóñora
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Juan
authors.initials: J
authors.lastname: Cristina
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay. Electronic address: pmoreno@cin.edu.uy.
authors.forename: Pilar
authors.initials: P
authors.lastname: Moreno
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D003906:Developing Countries; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D011487:Protein Conformation; D014583:Uruguay / Q000453:epidemiology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: DAAs; HCV variability; Resistance-associated variants