No HIV-1 molecular evolution on long-term antiretroviral therapy initiated during primary HIV-1 infection

AIDS. 2020 Oct 1;34(12):1745-1753. doi: 10.1097/QAD.0000000000002629.

Abstract

Objective: Most studies about HIV-1 molecular evolution have shown the lack of viral evolution on effective antiretroviral therapy (ART), although controversial results have been documented. We therefore aimed to look for evidence of HIV-1 evolution in patients who initiated ART at the time of primary HIV-1 infection (PHI).

Design: We included retrospectively 20 patients diagnosed at PHI, treated at the time of acute infection and with subsequent effective long-term suppressive ART (HIV viral load <20 copies/ml during at least 5 years without any blips).

Methods: Longitudinal blood samples were deep sequenced using Illumina Miseq. Drug-resistance-associated mutations were retained at 2% cutoff and interpreted using the latest Agence Nationale de Recherches sur le Sida et les Hépatites Virales resistance algorithm. Viral evolution was established when temporal structure on maximum-likelihood phylogenetic tree and significant change over time of HIV-1 genetic diversity measured as the average pairwise distance was observed.

Results: Emergences or disappearances of drug-resistance-associated mutations were detected in the blood cells during follow-up despite sustained virological control. In all patients, tree topologies showed an absence of segregation between sequences and blood viral populations from all time-points were intermingled. Comparison of the average pairwise distance showed the absence of significant viral diversity at the time of primary infection and afterwards during 5 years of full virological control under ART.

Conclusion: Despite a slight variation of minority resistance-associated mutation variants, there was no clear evidence of viral evolution during a prolonged period of time in this population of highly controlled adult patients treated at time of PHI.

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Evolution, Molecular
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Phylogeny
  • Retrospective Studies
  • Viral Load

Substances

  • Anti-HIV Agents