Both CD31(+) and CD31⁻ naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy

J Infect Dis. 2010 Dec 1;202(11):1738-48. doi: 10.1086/656721. Epub 2010 Oct 27.

Abstract

Background: Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31(+) and CD31⁻ naive T cells to immune reconstitution and viral persistence is unknown.

Methods: In a cross-sectional (n = 94) and longitudinal (n = 10) study of human immunodeficiency virus (HIV)-infected patients before and after ART, we examined the ratio of CD31(+) to CD31⁻ naive CD4(+) T cells. In the longitudinal cohort we then quantified the concentration of HIV-1 DNA in each cell subset and performed single-genome amplification of virus from memory and naive T cells.

Results: Patients receiving ART had a higher proportion of CD31(+) CD4(+) T cells than HIV-1-infected individuals naive to ART and uninfected control subjects (P < .001 and .007, respectively). After 24 months of ART, the proportion of CD31(+) naive CD4(+) T cells did not change, the concentration of HIV-1 DNA in memory CD4(+) T cells significantly decreased over time (P < .001), and there was no change in the concentration of HIV-1 DNA in CD31(+) or CD31⁻ naive CD4(+) T cells (P = .751 and .251, respectively). Single-genome amplification showed no evidence of virus compartmentalization in memory and naive T cell subsets before or after ART.

Conclusions: After ART, both CD31(+) and CD31⁻ naive CD4(+) T cells expand, and both subsets represent a stable, persistent reservoir of HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / pharmacology*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cross-Sectional Studies
  • Female
  • Flow Cytometry
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Longitudinal Studies
  • Male
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis*
  • Polymerase Chain Reaction
  • Regression Analysis
  • Singapur
  • Victoria

Substances

  • Anti-Retroviral Agents
  • Platelet Endothelial Cell Adhesion Molecule-1