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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.

Author information

1
Centre de Recherche du CHUM, Montréal, H2X0A9, QC, Canada.
2
Caprion Biosciences Inc., Montréal, H2X3Y7, QC, Canada.
3
Chronic Viral Illness Service and Division of Hematology, Research Institute, McGill University Health Centre, Montréal, H4A3J1, QC, Canada.
4
Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011, Lausanne, Switzerland.
5
Department of Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
6
Infectious Disease, Merck Research Laboratories, West Point, PA, 19486, USA.
7
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, 3000, Australia.
8
Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia.
9
Case Western Reserve University, Cleveland, OH, 44106, USA.
10
Centre de Recherche du CHUM, Montréal, H2X0A9, QC, Canada. nicolas.chomont@umontreal.ca.
11
Université de Montréal, Faculty of Medicine, Department of Microbiology, Infectiology and Immunology, Montréal, H3C3J7, QC, Canada. nicolas.chomont@umontreal.ca.

Abstract

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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