Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 str...

Autores
Sánchez, Daniela; Arazi Caillaud, Solange; Zapiola, Ines; Fernandez Giuliano, Silvina; Bologna, Rosa; Mangano, Andrea María Mercedes; Aulicino, Paula
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate.Materials and methods: HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses.Results: Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%),7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping.INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs.Conclusions: Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the useof INIs.
Fil: Sánchez, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina
Fil: Arazi Caillaud, Solange. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Fernandez Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mangano, Andrea María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aulicino, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
HIV
drug resistance
raltegravir
genotype determination
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:11336/239335
Acceder
id CONICETDig_def0e333509928ed46a585c38e0ae350
oai_identifier_str oai:ri.conicet.gov.ar:11336/239335
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strainsSánchez, DanielaArazi Caillaud, SolangeZapiola, InesFernandez Giuliano, SilvinaBologna, RosaMangano, Andrea María MercedesAulicino, PaulaHIVdrug resistanceraltegravirgenotype determinationhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate.Materials and methods: HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses.Results: Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%),7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping.INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs.Conclusions: Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the useof INIs.Fil: Sánchez, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; ArgentinaFil: Arazi Caillaud, Solange. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Fernandez Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mangano, Andrea María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Aulicino, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaOxford University Press2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/239335Sánchez, Daniela; Arazi Caillaud, Solange; Zapiola, Ines; Fernandez Giuliano, Silvina; Bologna, Rosa; et al.; Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains; Oxford University Press; Journal of Antimicrobial Chemotherapy; 75; 6; 6-2020; 1567-15740305-7453CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jac/article/75/6/1567/5775584info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dkaa042info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:45Zoai:ri.conicet.gov.ar:11336/239335instacron: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 09:47:45.547CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
title Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
spellingShingle Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
Sánchez, Daniela
HIV
drug resistance
raltegravir
genotype determination
title_short Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
title_full Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
title_fullStr Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
title_full_unstemmed Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
title_sort Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains
dc.creator.none.fl_str_mv Sánchez, Daniela
Arazi Caillaud, Solange
Zapiola, Ines
Fernandez Giuliano, Silvina
Bologna, Rosa
Mangano, Andrea María Mercedes
Aulicino, Paula
author Sánchez, Daniela
author_facet Sánchez, Daniela
Arazi Caillaud, Solange
Zapiola, Ines
Fernandez Giuliano, Silvina
Bologna, Rosa
Mangano, Andrea María Mercedes
Aulicino, Paula
author_role author
author2 Arazi Caillaud, Solange
Zapiola, Ines
Fernandez Giuliano, Silvina
Bologna, Rosa
Mangano, Andrea María Mercedes
Aulicino, Paula
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HIV
drug resistance
raltegravir
genotype determination
topic HIV
drug resistance
raltegravir
genotype determination
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate.Materials and methods: HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses.Results: Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%),7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping.INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs.Conclusions: Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the useof INIs.
Fil: Sánchez, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina
Fil: Arazi Caillaud, Solange. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Fernandez Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mangano, Andrea María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aulicino, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate.Materials and methods: HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses.Results: Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%),7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping.INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs.Conclusions: Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the useof INIs.
publishDate 2020
dc.date.none.fl_str_mv 2020-06
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/11336/239335
Sánchez, Daniela; Arazi Caillaud, Solange; Zapiola, Ines; Fernandez Giuliano, Silvina; Bologna, Rosa; et al.; Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains; Oxford University Press; Journal of Antimicrobial Chemotherapy; 75; 6; 6-2020; 1567-1574
0305-7453
CONICET Digital
CONICET
url http://hdl.handle.net/11336/239335
identifier_str_mv Sánchez, Daniela; Arazi Caillaud, Solange; Zapiola, Ines; Fernandez Giuliano, Silvina; Bologna, Rosa; et al.; Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains; Oxford University Press; Journal of Antimicrobial Chemotherapy; 75; 6; 6-2020; 1567-1574
0305-7453
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://academic.oup.com/jac/article/75/6/1567/5775584
info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dkaa042
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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