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

• Type of Material: Article
• Authors: Vijayakumar Velu, Emory University; Kehmia Titanji, Emory University; Hasan Ahmed,, Emory University; Ravi Dyavar Shetty, Emory University; Lakshmi S Chennareddi, Emory University; Gordon J Freeman, Dana-Farber Cancer Institute; Rafi Ahmed, Emory University; Rama Amara, Emory University
• Language: English
• Date: 2022-08-16
• Publisher: NATL ACAD SCIENCES
• Publication Version: Final Published Version
• Copyright Statement: © 2022 the Author(s). Published by PNAS.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.2202148119
• Title of Journal or Parent Work: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• Volume: 119
• Issue: 33
• Start Page: e2202148119
• End Page: e2202148119
• Grant/Funding Information: This work was supported by the NIH (R37AI112787 to R.R.A., P01AI056299 to G.J.F.), the NIH Office of Research Infrastructure Programs (P51 OD011132 to ENPRC), and Emory CFAR (P30 AI050409).
• Keywords: SIV; PD-1; HIV cure; HIV; Multidisciplinary Sciences; Science & Technology; Science & Technology - Other Topics; T-CELLS; AIDS

Abstract

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 antiretrovial 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.