Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in...

Autores
Sede, Mariano Miguel; Laufer, Natalia Lorna; Quarleri, Jorge Fabian
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This enhanced immunological pressure could favour the emergence of viral epitope variants able to evade immune surveillance and, when resistance-associated variants (RAVs) are implicated, could also be co-selected as a hitchhiking effect. This study analysed the dynamics of the frequency of protease and polymerase inhibitor RAVs that could affect future HCV treatment in human immunodeficiency virus (HIV) co-infected patients on stable antiretroviral therapy with previous IFN-based treatment failure. HCV genotype 1a RNA was extracted from plasma samples of 18 patients prior to and during (24 h and 4, 12, 24 and 48 weeks) therapy with peg-IFN+RBV. Next-generation sequencing was performed on HCV-RNA populations using NS3 and NS5B PCR-amplified coding regions. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima's D statistic. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (<5%), and in most cases their presence was not constant during follow-up. Only samples from two patients for each region exhibited Q80R/K/L and A421V as highly predominant variants. No significant differences were observed among sampling times for either π or D values. In conclusion, previous therapy and failure of peg-IFN+RBV were not associated with an increase in DAA-targeting NS3 or NS5B RAVs that naturally exist in HIV co-infected subjects.
Fil: Sede, Mariano Miguel. 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: Laufer, Natalia Lorna. 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: Quarleri, Jorge Fabian. 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
Hcv
Ns3
Ns5b
Peg-Ifn
Resistance-Associated Variants (Ravs)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38821
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patientsSede, Mariano MiguelLaufer, Natalia LornaQuarleri, Jorge FabianDirect-Acting AntiviralsHcvNs3Ns5bPeg-IfnResistance-Associated Variants (Ravs)https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This enhanced immunological pressure could favour the emergence of viral epitope variants able to evade immune surveillance and, when resistance-associated variants (RAVs) are implicated, could also be co-selected as a hitchhiking effect. This study analysed the dynamics of the frequency of protease and polymerase inhibitor RAVs that could affect future HCV treatment in human immunodeficiency virus (HIV) co-infected patients on stable antiretroviral therapy with previous IFN-based treatment failure. HCV genotype 1a RNA was extracted from plasma samples of 18 patients prior to and during (24 h and 4, 12, 24 and 48 weeks) therapy with peg-IFN+RBV. Next-generation sequencing was performed on HCV-RNA populations using NS3 and NS5B PCR-amplified coding regions. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima's D statistic. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (<5%), and in most cases their presence was not constant during follow-up. Only samples from two patients for each region exhibited Q80R/K/L and A421V as highly predominant variants. No significant differences were observed among sampling times for either π or D values. In conclusion, previous therapy and failure of peg-IFN+RBV were not associated with an increase in DAA-targeting NS3 or NS5B RAVs that naturally exist in HIV co-infected subjects.Fil: Sede, Mariano Miguel. 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: Laufer, Natalia Lorna. 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: Quarleri, Jorge Fabian. 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; ArgentinaElsevier Science2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38821Sede, Mariano Miguel; Laufer, Natalia Lorna; Quarleri, Jorge Fabian; Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients; Elsevier Science; International Journal of Antimicrobial Agents; 46; 2; 7-2015; 219-2240924-8579CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijantimicag.2015.04.011info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0924857915001880info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:23:46Zoai:ri.conicet.gov.ar:11336/38821instacron: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:34982025-10-15 15:23:46.511CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
title Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
spellingShingle Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
Sede, Mariano Miguel
Direct-Acting Antivirals
Hcv
Ns3
Ns5b
Peg-Ifn
Resistance-Associated Variants (Ravs)
title_short Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
title_full Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
title_fullStr Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
title_full_unstemmed Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
title_sort Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
dc.creator.none.fl_str_mv Sede, Mariano Miguel
Laufer, Natalia Lorna
Quarleri, Jorge Fabian
author Sede, Mariano Miguel
author_facet Sede, Mariano Miguel
Laufer, Natalia Lorna
Quarleri, Jorge Fabian
author_role author
author2 Laufer, Natalia Lorna
Quarleri, Jorge Fabian
author2_role author
author
dc.subject.none.fl_str_mv Direct-Acting Antivirals
Hcv
Ns3
Ns5b
Peg-Ifn
Resistance-Associated Variants (Ravs)
topic Direct-Acting Antivirals
Hcv
Ns3
Ns5b
Peg-Ifn
Resistance-Associated Variants (Ravs)
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This enhanced immunological pressure could favour the emergence of viral epitope variants able to evade immune surveillance and, when resistance-associated variants (RAVs) are implicated, could also be co-selected as a hitchhiking effect. This study analysed the dynamics of the frequency of protease and polymerase inhibitor RAVs that could affect future HCV treatment in human immunodeficiency virus (HIV) co-infected patients on stable antiretroviral therapy with previous IFN-based treatment failure. HCV genotype 1a RNA was extracted from plasma samples of 18 patients prior to and during (24 h and 4, 12, 24 and 48 weeks) therapy with peg-IFN+RBV. Next-generation sequencing was performed on HCV-RNA populations using NS3 and NS5B PCR-amplified coding regions. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima's D statistic. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (<5%), and in most cases their presence was not constant during follow-up. Only samples from two patients for each region exhibited Q80R/K/L and A421V as highly predominant variants. No significant differences were observed among sampling times for either π or D values. In conclusion, previous therapy and failure of peg-IFN+RBV were not associated with an increase in DAA-targeting NS3 or NS5B RAVs that naturally exist in HIV co-infected subjects.
Fil: Sede, Mariano Miguel. 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: Laufer, Natalia Lorna. 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: Quarleri, Jorge Fabian. 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 Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This enhanced immunological pressure could favour the emergence of viral epitope variants able to evade immune surveillance and, when resistance-associated variants (RAVs) are implicated, could also be co-selected as a hitchhiking effect. This study analysed the dynamics of the frequency of protease and polymerase inhibitor RAVs that could affect future HCV treatment in human immunodeficiency virus (HIV) co-infected patients on stable antiretroviral therapy with previous IFN-based treatment failure. HCV genotype 1a RNA was extracted from plasma samples of 18 patients prior to and during (24 h and 4, 12, 24 and 48 weeks) therapy with peg-IFN+RBV. Next-generation sequencing was performed on HCV-RNA populations using NS3 and NS5B PCR-amplified coding regions. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima's D statistic. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (<5%), and in most cases their presence was not constant during follow-up. Only samples from two patients for each region exhibited Q80R/K/L and A421V as highly predominant variants. No significant differences were observed among sampling times for either π or D values. In conclusion, previous therapy and failure of peg-IFN+RBV were not associated with an increase in DAA-targeting NS3 or NS5B RAVs that naturally exist in HIV co-infected subjects.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
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/11336/38821
Sede, Mariano Miguel; Laufer, Natalia Lorna; Quarleri, Jorge Fabian; Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients; Elsevier Science; International Journal of Antimicrobial Agents; 46; 2; 7-2015; 219-224
0924-8579
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38821
identifier_str_mv Sede, Mariano Miguel; Laufer, Natalia Lorna; Quarleri, Jorge Fabian; Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients; Elsevier Science; International Journal of Antimicrobial Agents; 46; 2; 7-2015; 219-224
0924-8579
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijantimicag.2015.04.011
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0924857915001880
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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