Resistance mutations of NS3 and NS5b in treatment-naïve patients infected with hepatitis C virus in Santa Catarina and Rio Grande do Sul states, Brazil.

Elisabete Andrade,Antonio G.P Ferreira,Marcela Fontana-Maurell,Marisa Ribeiro,Elaine Costa,Amilcar Tanuri,Patrícia Alvarez,Daniele Rocha,Daniela Tupy De Godoy,Rodrigo Brindeiro

doi:10.1590/1678-4685-gmb-2018-0237

Elisabete Andrade, Antonio G.P Ferreira + Show 8 more

Open Access

https://doi.org/10.1590/1678-4685-gmb-2018-0237

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Abstract

Hepatitis C virus (HCV) infection is a worldwide health problem. Nowadays, direct-acting antiviral agents (DAAs) are the main treatment for HCV; however, the high level of virus variability leads to the development of resistance-associated variants (RAVs). Thus, assessing RAVs in infected patients is important for monitoring treatment efficacy. The aim of our study was to investigate the presence of naturally occurring resistance mutations in HCV NS3 and NS5 regions in treatment-naïve patients. Ninety-six anti-HCV positive serum samples from blood donors at the Center of Hematology and Hemotherapy of Santa Catarina State (HEMOSC) were collected retrospectively in 2013 and evaluated in this study. HCV 1a (37.9%), 1b (25.3%), and 3a (36.8%) subtypes were found. The frequency of patients with RAVs in our study was 6.9%. The HCV NS5b sequencing reveled 1 sample with L320F mutation and 4 samples with the C316N/R polymorphism. The analysis of the NS3 region revealed the D168A/G/T (3.45%), S122G (1.15%), and V55A (2.3%) mutations. All samples from genotype 3a (36.8%) presented the V170 I/V non-synonymous mutation. In conclusion, we have shown that mutations in NS3 and NS5b genes are present in Brazilian isolates from therapy-naïve HCV patients.

Highlights

Hepatitis C virus (HCV) infection is a worldwide health problem
Genotype 1 (1a plus 1b) was the most frequent, followed by genotype 3, a result that is in agreement with what was previously reported in Brazil (Campiotto et al, 2005; Lampe et al, 2013; Nishiya et al, 2014)
Sixty-three samples were successfully geno- and subtyped by the NS3 and NS5b region, and there was no disagreement between the HCV genotypes in both regions

Summary

Introduction

Hepatitis C virus (HCV) infection is a worldwide health problem. The main antiviral treatment until 2011, was PEGylated interferon-alfa (aPeg-IFN) alone or in combination with ribavirin, leading to a sustained virological response (SVR) in 50% of treated patients, depending on the virus genotype causing the HCV infection (Peres-da-Silva et al, 2012; Paolucci et al, 2013; Gross et al, 2018). Direct-acting antiviral agents (DAAs) have been approved for HCV infection treatment, with an average SVR above 95%, at least for genotypes 1 and 4 (Leuw and Stephan, 2018). In Brazil, DAAs were incorporated by the Ministry of Health for the treatment of hepatitis C under the Unified Health System (SUS) since 2015 (Ministério da Saúde, 2018). There is little data about the efficacy of DAAs in Brazil, with some information found in the study by Sette Jr et al (2017)

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