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

  • Author(s): Fromentin, Rémi
  • DaFonseca, Sandrina
  • Costiniuk, Cecilia T
  • El-Far, Mohamed
  • Procopio, Francesco Andrea
  • Hecht, Frederick M
  • Hoh, Rebecca
  • Deeks, Steven G
  • Hazuda, Daria J
  • Lewin, Sharon R
  • Routy, Jean-Pierre
  • Sékaly, Rafick-Pierre
  • Chomont, Nicolas
  • et al.
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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