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dc.contributor.author
Sánchez, Daniela
dc.contributor.author
Arazi Caillaud, Solange
dc.contributor.author
Zapiola, Ines
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Fernandez Giuliano, Silvina
dc.contributor.author
Bologna, Rosa
dc.contributor.author
Mangano, Andrea María Mercedes
dc.contributor.author
Aulicino, Paula
dc.date.available
2024-07-08T13:21:53Z
dc.date.issued
2020-06
dc.identifier.citation
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
dc.identifier.issn
0305-7453
dc.identifier.uri
http://hdl.handle.net/11336/239335
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
HIV
dc.subject
drug resistance
dc.subject
raltegravir
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genotype determination
dc.subject.classification
Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.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
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-07-08T10:17:55Z
dc.journal.volume
75
dc.journal.number
6
dc.journal.pagination
1567-1574
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
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
dc.description.fil
Fil: Arazi Caillaud, Solange. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
dc.description.fil
Fil: Fernandez Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
dc.description.fil
Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Journal of Antimicrobial Chemotherapy
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jac/article/75/6/1567/5775584
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/jac/dkaa042
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