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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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

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Oxford University Press
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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.

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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

DeCS Terms

Compuestos heterocíclicos con 3 anillos
Farmacorresistencia viral
Infecciones por VIH
Inhibidores de integrasa VIH
Integrasa de VIH

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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.