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, Nicolas Chomont

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

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.

Original languageEnglish
Article number814
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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