Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals

PLoS Pathog. 2014 Aug 28;10(8):e1004345. doi: 10.1371/journal.ppat.1004345. eCollection 2014 Aug.

Abstract

A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Separation
  • DNA, Viral / analysis
  • Disease Progression
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Immunologic Memory / immunology*
  • Immunophenotyping
  • Oligonucleotide Array Sequence Analysis
  • Stem Cells / immunology
  • Stem Cells / virology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology
  • Viral Load
  • Viremia / immunology*
  • Viremia / virology

Substances

  • DNA, Viral