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

Rémi Fromentin, Sandrina DaFonseca, Cecilia T. Costiniuk, Mohamed El-Far, Francesco Andrea Procopio, Frederick M. Hecht, Rebecca Hoh, Steven G. Deeks, Daria J. Hazuda, Sharon R. Lewin, Jean-Pierre Routy, Rafick-Pierre Sékaly and Nicolas Chomont ()
Additional contact information
Rémi Fromentin: Centre de Recherche du CHUM
Sandrina DaFonseca: Caprion Biosciences Inc.
Cecilia T. Costiniuk: Chronic Viral Illness Service and Division of Hematology, Research Institute, McGill University Health Centre
Mohamed El-Far: Centre de Recherche du CHUM
Francesco Andrea Procopio: Lausanne University Hospital, University of Lausanne
Frederick M. Hecht: University of California San Francisco
Rebecca Hoh: University of California San Francisco
Steven G. Deeks: University of California San Francisco
Daria J. Hazuda: Merck Research Laboratories
Sharon R. Lewin: The University of Melbourne and Royal Melbourne Hospital
Jean-Pierre Routy: Chronic Viral Illness Service and Division of Hematology, Research Institute, McGill University Health Centre
Rafick-Pierre Sékaly: Case Western Reserve University
Nicolas Chomont: Centre de Recherche du CHUM

Nature Communications, 2019, vol. 10, issue 1, 1-7

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08798-7

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