The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32-CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term Virologic Suppression

J Infect Dis. 2019 Jan 1;219(1):80-88. doi: 10.1093/infdis/jiy461.

Abstract

Background: High-level expression of the Fcγ receptor, CD32hi, on CD4+ T cells was associated with enhanced human immunodeficiency virus (HIV) infection of the latent reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latent HIV reservoir in virally suppressed, perinatally HIV-infected adolescents.

Methods: The frequency of CD32hiCD4+ T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32hi and CD32-CD4+ T cells was quantified (N = 4) with a quantitative viral outgrowth assay. Viral outgrowth was measured by the standard p24 enzyme-linked immunosorbent assay and an ultrasensitive p24 assay (Simoa; Quanterix) with lower limits of quantitation.

Results: We found a 59.55-fold enrichment in the absolute number of infectious cells in the CD32- population compared with CD32hi cells. Exponential HIV replication occurred exclusively in CD32-CD4+ T cells (mean change, 17.46 pg/mL; P = .04). Induced provirus in CD32hiCD4+ T cells replicated to substantially lower levels, which did not increase significantly over time (mean change, 0.026 pg/mL; P = .23) and were detected only with the Simoa assay.

Conclusions: Our data suggests that the latent HIV reservoir resides mainly in CD32-CD4+ T cells in virally suppressed, perinatally HIV-infected adolescents, which has implications for reservoir elimination strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adolescent
  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1
  • Humans
  • Male
  • Receptors, IgG / immunology*
  • Virus Latency / immunology*
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Receptors, IgG