Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection

Autores
Esposito, Isabella; Marciano, Sebastián; Haddad, Leila; Galdame, Omar; Franco, Alejandra; Gadano, Adrián Carlos; Flichman, Diego Martin; Trinks, Julieta
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.
Fil: Esposito, Isabella. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Marciano, Sebastián. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Haddad, Leila. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Galdame, Omar. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Franco, Alejandra. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Gadano, Adrián Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Materia
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS
QUASISPECIES
RESISTANCE-ASSOCIATED SUBSTITUTIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87730
Acceder
id CONICETDig_589c92015e06c3437a6cb7bc40d1ba88
oai_identifier_str oai:ri.conicet.gov.ar:11336/87730
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infectionEsposito, IsabellaMarciano, SebastiánHaddad, LeilaGaldame, OmarFranco, AlejandraGadano, Adrián CarlosFlichman, Diego MartinTrinks, JulietaDIRECT-ACTING ANTIVIRALSHEPATITIS C VIRUSQUASISPECIESRESISTANCE-ASSOCIATED SUBSTITUTIONShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.Fil: Esposito, Isabella. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Marciano, Sebastián. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Haddad, Leila. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Galdame, Omar. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Franco, Alejandra. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Gadano, Adrián Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaMDPI AG2019-01-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87730Esposito, Isabella; Marciano, Sebastián; Haddad, Leila; Galdame, Omar; Franco, Alejandra; et al.; Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection; MDPI AG; Viruses; 11; 1; 21-1-2019; 1-181999-4915CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4915/11/1/3info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356817/info:eu-repo/semantics/altIdentifier/doi/10.3390/v11010003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:04Zoai:ri.conicet.gov.ar:11336/87730instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:05.009CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
title Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
spellingShingle Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
Esposito, Isabella
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS
QUASISPECIES
RESISTANCE-ASSOCIATED SUBSTITUTIONS
title_short Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
title_full Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
title_fullStr Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
title_full_unstemmed Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
title_sort Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection
dc.creator.none.fl_str_mv Esposito, Isabella
Marciano, Sebastián
Haddad, Leila
Galdame, Omar
Franco, Alejandra
Gadano, Adrián Carlos
Flichman, Diego Martin
Trinks, Julieta
author Esposito, Isabella
author_facet Esposito, Isabella
Marciano, Sebastián
Haddad, Leila
Galdame, Omar
Franco, Alejandra
Gadano, Adrián Carlos
Flichman, Diego Martin
Trinks, Julieta
author_role author
author2 Marciano, Sebastián
Haddad, Leila
Galdame, Omar
Franco, Alejandra
Gadano, Adrián Carlos
Flichman, Diego Martin
Trinks, Julieta
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS
QUASISPECIES
RESISTANCE-ASSOCIATED SUBSTITUTIONS
topic DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS
QUASISPECIES
RESISTANCE-ASSOCIATED SUBSTITUTIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.
Fil: Esposito, Isabella. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Marciano, Sebastián. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Haddad, Leila. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Galdame, Omar. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Franco, Alejandra. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina
Fil: Gadano, Adrián Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
description This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.
publishDate 2019
dc.date.none.fl_str_mv 2019-01-21
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/87730
Esposito, Isabella; Marciano, Sebastián; Haddad, Leila; Galdame, Omar; Franco, Alejandra; et al.; Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection; MDPI AG; Viruses; 11; 1; 21-1-2019; 1-18
1999-4915
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87730
identifier_str_mv Esposito, Isabella; Marciano, Sebastián; Haddad, Leila; Galdame, Omar; Franco, Alejandra; et al.; Prevalence and factors related to natural resistance-associated substitutions to direct-acting antivirals in patients with genotype 1 hepatitis C virus infection; MDPI AG; Viruses; 11; 1; 21-1-2019; 1-18
1999-4915
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4915/11/1/3
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356817/
info:eu-repo/semantics/altIdentifier/doi/10.3390/v11010003
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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