Publication: Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
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Identifiers
Date
2016-02-17
Authors
Brenner, Bluma G
Thomas, Rejean
Blanco, Jose Luis
Ibanescu, Ruxandra-Ilinca
Oliveira, Maureen
Mesplede, Thibault
Golubkov, Olga
Roger, Michel
Garcia, Federico
Martinez, Esteban
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Dolutegravir 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.
Description
MeSH Terms
Adult
Drug Resistance, Viral
Genotyping Techniques
HIV Infections
HIV Integrase
HIV Integrase Inhibitors
HIV-1
Heterocyclic Compounds, 3-Ring
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Mutation, Missense
Oxazines
Piperazines
Pyridones
Treatment Failure
Drug Resistance, Viral
Genotyping Techniques
HIV Infections
HIV Integrase
HIV Integrase Inhibitors
HIV-1
Heterocyclic Compounds, 3-Ring
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Mutation, Missense
Oxazines
Piperazines
Pyridones
Treatment Failure
DeCS Terms
Compuestos heterocíclicos con 3 anillos
Farmacorresistencia viral
Infecciones por VIH
Inhibidores de integrasa VIH
Integrasa de VIH
Farmacorresistencia viral
Infecciones por VIH
Inhibidores de integrasa VIH
Integrasa de VIH
CIE Terms
Keywords
HIV Integrase Inhibitors, Heterocyclic Compounds, 3-Ring, Oxazines, Piperazines, Pyridones
Citation
Brenner 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.