PD-1 blockade following ART interruption enhances control of pathogenic SIV in rhesus macaques

Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2202148119. doi: 10.1073/pnas.2202148119. Epub 2022 Aug 8.


Programmed death-1 (PD-1) blockade during chronic Simian immunodeficiency virus (SIV) infection results in restoration of CD8 T-cell function and enhances viral control. Here, we tested the therapeutic benefits of PD-1 blockade administered soon after anti-retrovial therapy (ART) interruption (ATI) by treating SIV-infected and ART-suppressed macaques with either an anti-PD-1 antibody (n = 7) or saline (n = 4) at 4 wk after ATI. Following ATI, the plasma viremia increased rapidly in all animals, and the frequency of SIV-specific CD8 T cells also increased in some animals. PD-1 blockade post ATI resulted in higher proliferation of total memory CD8 and CD4 T cells and natural killer cells. PD-1 blockade also resulted in higher proliferation of SIV-specific CD8 T cells and promoted their differentiation toward better functional quality. Importantly, four out of the seven anti-PD-1 antibody-treated animals showed a rapid decline in plasma viremia by 100- to 2300-fold and this was observed only in animals that showed measurable SIV-specific CD8 T cells post PD-1 blockade. These results demonstrate that PD-1 blockade following ATI can significantly improve the function of anti-viral CD8 T cells and enhance viral control and strongly suggests its potential synergy with other immunotherapies that induce functional CD8 T-cell response under ART. These results have important implications for HIV cure research.

Keywords: HIV; HIV cure; PD-1; SIV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Retroviral Agents* / therapeutic use
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / virology
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunologic Memory
  • Macaca mulatta
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Simian Acquired Immunodeficiency Syndrome* / drug therapy
  • Simian Acquired Immunodeficiency Syndrome* / immunology
  • Simian Immunodeficiency Virus* / drug effects
  • Viral Load / drug effects
  • Viremia / drug therapy


  • Anti-Retroviral Agents
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor