title: 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.
abstract: 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.
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Emmanouil
authors: E
authors: Papasavvas
authors: School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
authors: Andrea
authors: A
authors: Foulkes
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Xiangfan
authors: X
authors: Yin
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Jocelin
authors: J
authors: Joseph
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Brian
authors: B
authors: Ross
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Livio
authors: L
authors: Azzoni
authors: Presbyterian Hospital-University of Pennsylvania Hospital, Philadelphia, PA, USA.
authors: Jay R
authors: JR
authors: Kostman
authors: Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, PA, USA.
authors: Karam
authors: K
authors: Mounzer
authors: Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, PA, USA.
authors: Jane
authors: J
authors: Shull
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Luis J
authors: LJ
authors: Montaner
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008875:Middle Aged; D054353:Perforin / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D017252:CD3 Complex; D052118:Lysosomal-Associated Membrane Protein 1; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D054353:Perforin; D007371:Interferon-gamma
keywords: HIV-specific CD8+ T cells; antiretroviral therapy interruption; plasmacytoid dendritic cells; set-point viral load