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Nat Commun. 2019 Feb 18;10(1):814. doi: 10.1038/s41467-019-08798-7.

PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals.

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Centre de Recherche du CHUM, Montréal, H2X0A9, QC, Canada.
Caprion Biosciences Inc., Montréal, H2X3Y7, QC, Canada.
Chronic Viral Illness Service and Division of Hematology, Research Institute, McGill University Health Centre, Montréal, H4A3J1, QC, Canada.
Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011, Lausanne, Switzerland.
Department of Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Infectious Disease, Merck Research Laboratories, West Point, PA, 19486, USA.
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, 3000, Australia.
Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia.
Case Western Reserve University, Cleveland, OH, 44106, USA.
Centre de Recherche du CHUM, Montréal, H2X0A9, QC, Canada.
Université de Montréal, Faculty of Medicine, Department of Microbiology, Infectiology and Immunology, Montréal, H3C3J7, QC, Canada.


HIV persists in latently infected CD4+ T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4+ T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.

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