Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs

J Antimicrob Chemother. 2018 Apr 1;73(4):1045-1053. doi: 10.1093/jac/dkx475.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Female
  • Genetic Variation*
  • Genotype
  • HIV Envelope Protein gp120 / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Integrase / genetics
  • HIV Integrase Inhibitors / administration & dosage*
  • HIV-1 / classification*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Heterocyclic Compounds, 3-Ring / administration & dosage*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Prospective Studies
  • Pyridones
  • Sequence Analysis, DNA
  • Treatment Outcome
  • Young Adult


  • DNA, Viral
  • HIV Envelope Protein gp120
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • gp120 protein, Human immunodeficiency virus 1
  • dolutegravir
  • HIV Integrase

Associated data