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Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.

dc.contributor.authorBrenner, Bluma G
dc.contributor.authorThomas, Rejean
dc.contributor.authorBlanco, Jose Luis
dc.contributor.authorIbanescu, Ruxandra-Ilinca
dc.contributor.authorOliveira, Maureen
dc.contributor.authorMesplede, Thibault
dc.contributor.authorGolubkov, Olga
dc.contributor.authorRoger, Michel
dc.contributor.authorGarcia, Federico
dc.contributor.authorMartinez, Esteban
dc.contributor.authorWainberg, Mark A
dc.contributor.funderCanadian Institutes for Health Research (CIHR)
dc.contributor.funderFonds de Recherche du Que´bec-Sante´ (FRQS)-Re´seau SIDA
dc.contributor.funderLarge-Scale Applied Research Project in Genomics and Personalized Health HIV142 contract from Genome Canada to M
dc.date.accessioned2023-01-25T08:31:33Z
dc.date.available2023-01-25T08:31:33Z
dc.date.issued2016-02-17
dc.description.abstractDolutegravir shows a high barrier to resistance with no previously reported cases of acquired integrase mutations during first-line therapy. In this study, rapid development of the G118R mutation arose following a switch from first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to dolutegravir monotherapy. The G118R mutation also arose in a treatment-experienced patient switched to dolutegravir monotherapy. The genetic basis for G118R selection and potential phenotypic outcome was ascertained. Genotypic analysis was performed on patients with virological failure ( We report on two patients who developed viral failure while on dolutegravir monotherapy. Both patients had been on a current or previous regimen containing integrase inhibitors. Virological failure ( Although resistance to dolutegravir is typically rare, genetic polymorphisms and monotherapy can facilitate the acquisition of G118R.
dc.description.sponsorshipThis work was supported by grants from the Canadian Institutes for Health Research (CIHR) and Fonds de Recherche du Que´bec-Sante´ (FRQS)-Re´seau SIDA, and a Large-Scale Applied Research Project in Genomics and Personalized Health HIV142 contract from Genome Canada to M. W. The funders played no decision-making role in the design, execution, and analysis or reporting of the research.
dc.description.versionSi
dc.identifier.citationBrenner BG, Thomas R, Blanco JL, Ibanescu RI, Oliveira M, Mesplède T, et al. Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. J Antimicrob Chemother. 2016 Jul;71(7):1948-53.
dc.identifier.doi10.1093/jac/dkw071
dc.identifier.essn1460-2091
dc.identifier.pmcPMC4896408
dc.identifier.pmid27029845
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896408/pdf
dc.identifier.unpaywallURLhttps://academic.oup.com/jac/article-pdf/71/7/1948/11281997/dkw071.pdf
dc.identifier.urihttp://hdl.handle.net/10668/9956
dc.issue.number7
dc.journal.titleThe Journal of antimicrobial chemotherapy
dc.journal.titleabbreviationJ Antimicrob Chemother
dc.language.isoen
dc.organizationHospital Universitario San Cecilio
dc.organizationInstituto de Investigación Biosanitaria ibs. GRANADA
dc.page.number1948-53
dc.publisherOxford University Press
dc.pubmedtypeCase Reports
dc.pubmedtypeJournal Article
dc.relation.projectIDHIV142
dc.relation.publisherversionhttps://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkw071
dc.rights.accessRightsopen access
dc.subjectHIV Integrase Inhibitors
dc.subjectHeterocyclic Compounds, 3-Ring
dc.subjectOxazines
dc.subjectPiperazines
dc.subjectPyridones
dc.subject.decsCompuestos heterocíclicos con 3 anillos
dc.subject.decsFarmacorresistencia viral
dc.subject.decsInfecciones por VIH
dc.subject.decsInhibidores de integrasa VIH
dc.subject.decsIntegrasa de VIH
dc.subject.meshAdult
dc.subject.meshDrug Resistance, Viral
dc.subject.meshGenotyping Techniques
dc.subject.meshHIV Infections
dc.subject.meshHIV Integrase
dc.subject.meshHIV Integrase Inhibitors
dc.subject.meshHIV-1
dc.subject.meshHeterocyclic Compounds, 3-Ring
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMicrobial Sensitivity Tests
dc.subject.meshMiddle Aged
dc.subject.meshMutation, Missense
dc.subject.meshOxazines
dc.subject.meshPiperazines
dc.subject.meshPyridones
dc.subject.meshTreatment Failure
dc.titleDevelopment of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number71
dspace.entity.typePublication

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