Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs

Elife. 2015 Oct 6:4:e09115. doi: 10.7554/eLife.09115.

Abstract

Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.

Keywords: HIV-1 reservoir; early long-term ART; human; infectious disease; long-term non-progressors; microbiology; seroconversion; viruses.

Publication types

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

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Blood / virology
  • Cross-Sectional Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology*
  • HIV-1 / isolation & purification*
  • Humans
  • Male
  • Middle Aged
  • Proviruses / isolation & purification
  • Rectum / virology
  • Secondary Prevention
  • Treatment Outcome
  • Viral Load*

Substances

  • Anti-Retroviral Agents

Grants and funding

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