Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/59115 |
Resumo: | Relevant resistance-associated substitutions (RASs) to elbasvir, the new HCV NS5A inhibitor, may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are few data outside clinical trials evaluating their prevalence and impact of elbasvir/grazoprevir. A multicenter cross-sectional study of 617 HCV-GT1a-infected individuals attended in 84 Spanish hospitals from the 17 Autonomous Communities and two Autonomous cities was performed. HCV population sequencing was used to identify RASs to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-GT1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%; respectively). Only 3.4% of patients had viruses with RASs that confer reduced susceptibility to elbasvir by geno2pheno[HCV] that identified exclusively the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations considered as RASs to elbasvir. Lower prevalence of RASs to elbasvir in our HCV-GT1a-Spanish cohort was observed than reported previously in clinical trials. This information may be essential to guiding the implementation of elbasvir/grazoprevir in Spain, expected at the beginning of 2017 and the management of GT1a-infected patients. |
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Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional studyRelevant resistance-associated substitutions (RASs) to elbasvir, the new HCV NS5A inhibitor, may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are few data outside clinical trials evaluating their prevalence and impact of elbasvir/grazoprevir. A multicenter cross-sectional study of 617 HCV-GT1a-infected individuals attended in 84 Spanish hospitals from the 17 Autonomous Communities and two Autonomous cities was performed. HCV population sequencing was used to identify RASs to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-GT1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%; respectively). Only 3.4% of patients had viruses with RASs that confer reduced susceptibility to elbasvir by geno2pheno[HCV] that identified exclusively the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations considered as RASs to elbasvir. Lower prevalence of RASs to elbasvir in our HCV-GT1a-Spanish cohort was observed than reported previously in clinical trials. This information may be essential to guiding the implementation of elbasvir/grazoprevir in Spain, expected at the beginning of 2017 and the management of GT1a-infected patients.The authors would like to thank all the centers and investigators involved in Spanish Group of Chronic Viral Hepatitis (see Supplemental Data) and patients for their participation and the clinical samples provided. This work was supported by grants from ‘Instituto de Salud Carlos III’ (Ref. PI14CIII/00011 to SR, MPY 1039/14 and PI15CIII/00031 to VB). CP is supported by the Portuguese ‘Fundação para a Ciência e Tecnologia’ (FCT) (grant number SFRH/BPD/77448/2011, part of the EDCTP2 program supported by the European Union). VB is supported by the Miguel Servet program run by the ‘Fondo de Investigación Sanitaria’ (ISCIII) (grant number CP13/00098). MAJS is supported by ‘Instituto de Salud Carlos III’ (grant numbers CD13/00013).Springer NatureRepositório da Universidade de LisboaPalladino, ClaudiaSánchez-Carrillo, MartaMaté-Cano, IreneVázquez-Morón, SoniaJimenez-Sousa, Maria ÁngelesGutiérrez-Rivas, MónicaResino, SalvadorBriz, Verónica2023-08-31T20:27:39Z20172023-02-09T15:01:39Z2017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/59115engPalladino C, Sánchez-Carrillo M, Mate-Cano I, Vázquez-Morón S, Jimenez-Sousa MÁ, Gutiérrez-Rivas M, et al. Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study. Sci Rep [Internet]. 6 de junho de 2017;7(1):2892. Disponível em: https://www.nature.com/articles/s41598-017-02968-7cv-prod-118552610.1038/s41598-017-02968-72-s2.0-85020415072info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:03:43Zoai:repositorio.ul.pt:10451/59115Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:48.329174Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
title |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
spellingShingle |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study Palladino, Claudia |
title_short |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
title_full |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
title_fullStr |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
title_full_unstemmed |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
title_sort |
Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: A cross-sectional study |
author |
Palladino, Claudia |
author_facet |
Palladino, Claudia Sánchez-Carrillo, Marta Maté-Cano, Irene Vázquez-Morón, Sonia Jimenez-Sousa, Maria Ángeles Gutiérrez-Rivas, Mónica Resino, Salvador Briz, Verónica |
author_role |
author |
author2 |
Sánchez-Carrillo, Marta Maté-Cano, Irene Vázquez-Morón, Sonia Jimenez-Sousa, Maria Ángeles Gutiérrez-Rivas, Mónica Resino, Salvador Briz, Verónica |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Palladino, Claudia Sánchez-Carrillo, Marta Maté-Cano, Irene Vázquez-Morón, Sonia Jimenez-Sousa, Maria Ángeles Gutiérrez-Rivas, Mónica Resino, Salvador Briz, Verónica |
description |
Relevant resistance-associated substitutions (RASs) to elbasvir, the new HCV NS5A inhibitor, may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are few data outside clinical trials evaluating their prevalence and impact of elbasvir/grazoprevir. A multicenter cross-sectional study of 617 HCV-GT1a-infected individuals attended in 84 Spanish hospitals from the 17 Autonomous Communities and two Autonomous cities was performed. HCV population sequencing was used to identify RASs to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-GT1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%; respectively). Only 3.4% of patients had viruses with RASs that confer reduced susceptibility to elbasvir by geno2pheno[HCV] that identified exclusively the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations considered as RASs to elbasvir. Lower prevalence of RASs to elbasvir in our HCV-GT1a-Spanish cohort was observed than reported previously in clinical trials. This information may be essential to guiding the implementation of elbasvir/grazoprevir in Spain, expected at the beginning of 2017 and the management of GT1a-infected patients. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2023-08-31T20:27:39Z 2023-02-09T15:01:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/59115 |
url |
http://hdl.handle.net/10451/59115 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Palladino C, Sánchez-Carrillo M, Mate-Cano I, Vázquez-Morón S, Jimenez-Sousa MÁ, Gutiérrez-Rivas M, et al. Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study. Sci Rep [Internet]. 6 de junho de 2017;7(1):2892. Disponível em: https://www.nature.com/articles/s41598-017-02968-7 cv-prod-1185526 10.1038/s41598-017-02968-7 2-s2.0-85020415072 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Springer Nature |
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Springer Nature |
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