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Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain

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Resumo:Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
Autores principais:Palladino, Claudia
Outros Autores:Ezeonwumelu, Ifeanyi J.; Maté, Irene; Borrego, Pedro; Martínez-Román, Paula; Arca-Lafuente, Sonia; Resino, Salvador; Taveira, Nuno; Briz, Verónica
Ano:2020
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
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author Palladino, Claudia
author2 Ezeonwumelu, Ifeanyi J.
Maté, Irene
Borrego, Pedro
Martínez-Román, Paula
Arca-Lafuente, Sonia
Resino, Salvador
Taveira, Nuno
Briz, Verónica
author2_role author
author
author
author
author
author
author
author
author_facet Palladino, Claudia
Ezeonwumelu, Ifeanyi J.
Maté, Irene
Borrego, Pedro
Martínez-Román, Paula
Arca-Lafuente, Sonia
Resino, Salvador
Taveira, Nuno
Briz, Verónica
author_role author
contributor_name_str_mv Repositório Científico de Acesso Aberto da ULisboa
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datacite.creators.creator.creatorName.fl_str_mv Palladino, Claudia
Ezeonwumelu, Ifeanyi J.
Maté, Irene
Borrego, Pedro
Martínez-Román, Paula
Arca-Lafuente, Sonia
Resino, Salvador
Taveira, Nuno
Briz, Verónica
datacite.date.Accepted.fl_str_mv 2020-12-01T00:00:00Z
datacite.date.available.fl_str_mv 2023-08-31T13:35:52Z
datacite.date.embargoed.fl_str_mv 2023-08-31T13:35:52Z
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datacite.titles.title.fl_str_mv Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
dc.contributor.none.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
dc.creator.none.fl_str_mv Palladino, Claudia
Ezeonwumelu, Ifeanyi J.
Maté, Irene
Borrego, Pedro
Martínez-Román, Paula
Arca-Lafuente, Sonia
Resino, Salvador
Taveira, Nuno
Briz, Verónica
dc.date.Accepted.fl_str_mv 2020-12-01T00:00:00Z
dc.date.available.fl_str_mv 2023-08-31T13:35:52Z
dc.date.embargoed.fl_str_mv 2023-08-31T13:35:52Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10451/59104
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Springer Nature
dc.rights.cclincense.fl_str_mv http://creativecommons.org/licenses/by/4.0/
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.title.fl_str_mv Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
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person_str_mv Palladino, Claudia
Palladino, Claudia
https://www.ciencia-id.pt/721D-6851-20D5
721D-6851-20D5
http://orcid.org/0000-0002-8148-0928
0000-0002-8148-0928
Ezeonwumelu, Ifeanyi J.
Ezeonwumelu, Ifeanyi J.
http://orcid.org/0000-0003-4007-2212
0000-0003-4007-2212
Maté, Irene
Maté, Irene
http://orcid.org/0000-0002-9045-9581
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Borrego, Pedro
Borrego, Pedro
https://www.ciencia-id.pt/A71C-0177-722F
A71C-0177-722F
http://orcid.org/0000-0002-1949-9484
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Martínez-Román, Paula
Arca-Lafuente, Sonia
Arca-Lafuente, Sonia
http://orcid.org/0000-0003-4750-0988
0000-0003-4750-0988
Resino, Salvador
Resino, Salvador
http://orcid.org/0000-0001-8783-0450
0000-0001-8783-0450
Taveira, Nuno
Taveira, Nuno
https://www.ciencia-id.pt/7111-3383-A926
7111-3383-A926
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Briz, Verónica
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publishDate 2020
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spelling engSpringer Naturept_PTHepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.application/pdfpt_PTEpidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in SpainPersonalPalladino, ClaudiaDSpacehttp://dspace.org/items/96b2385b-89f4-428a-9ab2-6fdb5514541bDSpacehttp://dspace.org/items/96b2385b-89f4-428a-9ab2-6fdb5514541bPalladinoClaudiaCiência IDhttps://www.ciencia-id.pt721D-6851-20D5ORCIDhttp://orcid.org0000-0002-8148-0928PersonalEzeonwumelu, Ifeanyi J.DSpacehttp://dspace.org/items/124ca7f9-fbba-4c7a-a77b-ecda48de1bb0DSpacehttp://dspace.org/items/124ca7f9-fbba-4c7a-a77b-ecda48de1bb0EzeonwumeluIfeanyiORCIDhttp://orcid.org0000-0003-4007-2212Researcher IDhttps://www.researcherid.comP-9428-2017Researcher IDhttps://www.researcherid.comGQP-0394-2022Scopus Author IDhttps://www.scopus.com57203432749PersonalMaté, IreneDSpacehttp://dspace.org/items/3145c0e5-1ca2-4bdf-b103-9e79218b07cdDSpacehttp://dspace.org/items/3145c0e5-1ca2-4bdf-b103-9e79218b07cdMatéIreneORCIDhttp://orcid.org0000-0002-9045-9581PersonalBorrego, PedroDSpacehttp://dspace.org/items/64f9a682-4d1d-4bc3-8854-c6673527f871DSpacehttp://dspace.org/items/64f9a682-4d1d-4bc3-8854-c6673527f871BorregoPedroCiência IDhttps://www.ciencia-id.ptA71C-0177-722FORCIDhttp://orcid.org0000-0002-1949-9484Researcher IDhttps://www.researcherid.comH-6968-2013Scopus Author IDhttps://www.scopus.com25225039400Martínez-Román, PaulaPersonalArca-Lafuente, SoniaDSpacehttp://dspace.org/items/c082ff9e-3d28-42ce-b50a-b23d5a4417a2DSpacehttp://dspace.org/items/c082ff9e-3d28-42ce-b50a-b23d5a4417a2Arca de LafuenteSoniaORCIDhttp://orcid.org0000-0003-4750-0988Researcher IDhttps://www.researcherid.comA-7807-2019PersonalResino, SalvadorDSpacehttp://dspace.org/items/a428ce68-f89c-4f34-af69-04b11f8717caDSpacehttp://dspace.org/items/a428ce68-f89c-4f34-af69-04b11f8717caResinoSalvadorORCIDhttp://orcid.org0000-0001-8783-0450PersonalTaveira, NunoDSpacehttp://dspace.org/items/d62b22f8-7ce6-4bb2-ac55-2117707f6612DSpacehttp://dspace.org/items/d62b22f8-7ce6-4bb2-ac55-2117707f6612TaveiraNunoCiência IDhttps://www.ciencia-id.pt7111-3383-A926ORCIDhttp://orcid.org0000-0003-0176-5585PersonalBriz, VerónicaDSpacehttp://dspace.org/items/4612acdd-e150-40d9-9989-a372cfee3499DSpacehttp://dspace.org/items/4612acdd-e150-40d9-9989-a372cfee3499BrizVerónicaORCIDhttp://orcid.org0000-0003-2297-5098Researcher IDhttps://www.researcherid.comT-4183-2017Scopus Author IDhttps://www.scopus.com9332849600HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptDOIIsPartOf10.1038/s41598-020-69692-72023-08-31T13:35:52Z2020-122023-02-03T16:40:01Z2020-12-01T00:00:00ZHandlehttp://hdl.handle.net/10451/59104http://purl.org/coar/access_right/c_abf2open access2260518 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2020-12http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/f2090f69-c5e5-4243-8a89-2bb71bb2f816/downloadScientific Reports10113024
spellingShingle Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
Palladino, Claudia
status SINGLETON
title Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
title_full Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
title_fullStr Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
title_full_unstemmed Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
title_short Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
title_sort Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
url http://hdl.handle.net/10451/59104
visible 1