Establishment and stability of the latent HIV-1 DNA reservoir

Elife. 2016 Nov 15;5:e18889. doi: 10.7554/eLife.18889.

Abstract

HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3-18 years of suppressive ART. A median of 14% (range 0-42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.

Keywords: HIV; cure; evolution; infectious disease; microbiology; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Virus Latency*

Substances

  • Anti-Retroviral Agents
  • DNA, Viral

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.