Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4 + T cells

Nat Med. 2017 Jul;23(7):885-889. doi: 10.1038/nm.4347. Epub 2017 May 29.

Abstract

Although antiretroviral therapy can suppress HIV-1 infection to undetectable levels of plasma viremia, integrated latent HIV-1 genomes that encode replication-competent virus persist in resting CD4+ T cells. This latent HIV-1 reservoir represents a major barrier to a cure. Currently, there are substantial efforts to identify therapeutic approaches that will eliminate or reduce the size of this latent HIV-1 reservoir. In this regard, a sensitive assay that can accurately and rapidly quantify inducible, replication-competent latent HIV-1 from resting CD4+ T cells is essential for HIV-1 eradication studies. Here we describe a reporter cell-based assay to quantify inducible, replication-competent latent HIV-1. This assay has several advantages over existing technology in that it (i) is sensitive; (ii) requires only a small blood volume; (iii) is faster, less labor intensive, and less expensive; and (iv) can be readily adapted into a high-throughput format. Using this assay, we show that the size of the inducible latent HIV-1 reservoir in aviremic participants on therapy is approximately 70-fold larger than previous estimates.

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / virology*
  • DNA, Viral / analysis*
  • Female
  • Fusion Proteins, gag-pol / genetics
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / analysis*
  • Viral Load / methods*
  • Virus Latency

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Fusion Proteins, gag-pol
  • RNA, Viral