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Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs.

Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs.
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Gantner P, Lee GQ, Rey D, Mesplede T, Partisani M, Cheneau C, Beck-Wirth G, Faller JP, Mohseni-Zadeh M, Martinot M, Wainberg MA, Fafi-Kremer S,


Gantner P, Lee GQ, Rey D, Mesplede T, Partisani M, Cheneau C, Beck-Wirth G, Faller JP, Mohseni-Zadeh M, Martinot M, Wainberg MA, Fafi-Kremer S, (click to view)

Gantner P, Lee GQ, Rey D, Mesplede T, Partisani M, Cheneau C, Beck-Wirth G, Faller JP, Mohseni-Zadeh M, Martinot M, Wainberg MA, Fafi-Kremer S,

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The Journal of antimicrobial chemotherapy 2017 12 13() doi 10.1093/jac/dkx475

Abstract
Objectives
Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen.

Methods
Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5). The integrase and V3 loop regions of HIV-1 DNA isolated from PBMCs were analysed by pyrosequencing at baseline and weeks 4, 24 and 48. HIV-1 genetic diversity was calculated using Shannon entropy.

Results
All individuals achieved or maintained viral suppression throughout the study. A low and stable genetic diversity of archived HIV quasispecies was observed in individuals starting treatment during acute infection. A dramatic reduction of the genetic diversity was observed at week 4 of treatment in the other individuals. In these patients and despite virological suppression, a recovery of the genetic diversity of the reservoirs was observed up to 48 weeks. Viral variants bearing dolutegravir resistance-associated substitutions at integrase position 50, 124, 230 or 263 were detected in five individuals (n = 5/20, 25%) from all groups except those who were ART-failing at baseline. None of these substitutions led to virological failure.

Conclusions
These data demonstrate that the genetic diversity of the HIV-1 reservoir is reshaped following the initiation of a dolutegravir-based regimen and strongly suggest that HIV-1 can continue to replicate despite successful treatment.

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