Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1(+) patients

Immunology. 2015 Jul;145(3):380-90. doi: 10.1111/imm.12452. Epub 2015 May 19.


The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1(+) patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3(+) CD4(-) perforin(+) IFN-γ(+) cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R(2) = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3(+) CD4(-) CSFE(lo) CD107a(+) cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies.

Keywords: HIV-specific CD8+ T cells; antiretroviral therapy interruption; plasmacytoid dendritic cells; set-point viral load.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interferon-gamma / immunology
  • Lysosomal-Associated Membrane Protein 1 / immunology
  • Middle Aged
  • Perforin / immunology
  • Protein Precursors / immunology*
  • Retrospective Studies
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Time Factors
  • Treatment Outcome
  • Viral Load / drug effects
  • Viral Load / immunology*


  • Anti-HIV Agents
  • CD3 Complex
  • Lysosomal-Associated Membrane Protein 1
  • Protein Precursors
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • Perforin
  • Interferon-gamma