Author | Costa, Vanessa D. | |
Author | Mello, Carlos E. Brandão | |
Author | Nunes, Estevão P. | |
Author | Silva, Pedro Guilherme Corôa dos Santos | |
Author | Ximenes, Lia Laura L. | |
Author | Lampe, Elisabeth | |
Author | Mello, Francisco Campello do Amaral | |
Access date | 2019-08-29T11:51:26Z | |
Available date | 2019-08-29T11:51:26Z | |
Document date | 2019 | |
Citation | COSTA, Vanessa D. et al. Treatment of chronic HCV infection with DAAs in Rio de Janeiro/Brazil: SVR rates and baseline resistance analyses in NS5A and NS5B genes. Plos One, v. 14, n. 5, p. 1-12, May 2019. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/35176 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | |
Subject in Portuguese | Infecção crônica | pt_BR |
Subject in Portuguese | Antivirais orais de ação direta | pt_BR |
Subject in Portuguese | HCV | pt_BR |
Subject in Portuguese | Gene NS5A | pt_BR |
Subject in Portuguese | Gene NS5B | pt_BR |
Subject in Portuguese | Resposta virológica sustentada | pt_BR |
Subject in Portuguese | Resistência | pt_BR |
Subject in Portuguese | Rio de Janeiro | pt_BR |
Title | Treatment of chronic HCV infection with DAAs in Rio de Janeiro/Brazil: SVR rates and baseline resistance analyses in NS5A and NS5B genes | pt_BR |
Type | Article | |
DOI | 10.1371/journal.pone.0216327 | |
Abstract | The selection of viral strains with resistance-associated substitutions at hepatitis C virus (HCV) NS5A and NS5B genes is considered one of the limiting factors for achieving sustained virologic response (SVR) to combination of direct-acting antivirals daclatasvir (DCV) and sofosbuvir (SOF). Since 2015, this interferon-free regimen has been available in Brazilian clinical routine for treating mono- and HCV/HIV-coinfected patients chronically infected with genotypes 1 and 3. Our aim was to assess SVR rate for Brazilian patients chronically infected with genotypes 1 and 3 after DCV/SOF therapy and the frequency of baseline RASs in HCV NS5A and NS5B genes. Serum samples were collected from 107 monoinfected patients and 25 HCV/HIV co-infected patients before antiviral therapy with DCV/ SOF. Genetic diversity of NS5A and NS5B genes was assessed by direct nucleotide sequencing. Overall, SVR rate was 95.4% (126/132), and treatment failure occurred in five monoinfected and one HCV/HIV co-infected patient. NS5A RASs frequency was higher for HCV/HIV patients (28%) than monoinfected patients (16.8%). No difference was evidenced
between mono- and HCV/HIV-coinfected groups (15% vs. 16%) regarding NS5B gene. Genotype (GT) 1b strains had significantly more baseline substitutions in NS5A (31.6%) than GT 1a and 3a. At least one primary NS5A RAS described in literature at loci 28, 30, 31 or 93 was identified in HCV GTs 1 strains for both groups. As for NS5B, RASs at positions 159 and 316 was observed only in GT 1b strains. This study highlighted that SVR rate in clinical routine in Brazil was similar to randomized clinical trials (89–98%). Our research provided genetic data about the circulation of resistant variants in Brazil. Despite its presence, most of identified baseline mutations did not negatively impact treatment outcome. Genetic diversity of circulating strains suggested that most of the Brazilian HCV chronic carriers are
susceptible to new therapeutic regimens including recently approved DAAs. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffrée e Guinle. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Chronic HCV infection | pt_BR |
Subject | Treatment | pt_BR |
Subject | DAAS | pt_BR |
Subject | SRV | pt_BR |
Subject | Resistance analyses | pt_BR |
Subject | Rio de Janeiro | pt_BR |
Subject | Brazil | pt_BR |
Subject | Gene NS5A | pt_BR |
Subject | Gene NS5B | pt_BR |