TY - JOUR AU - Mylvaganam, Geetha H. AU - Chea, Lynette S. AU - Tharp, Gregory K. AU - Hicks, Sakeenah AU - Velu, Vijayakumar AU - Iyer, Smita S. AU - Deleage, Claire AU - Estes, Jacob D. AU - Bosinger, Steven E. AU - Freeman, Gordon J. AU - Ahmed, Rafi AU - Amara, Rama R. T1 - Combination anti–PD-1 and antiretroviral therapy provides therapeutic benefit against SIV PY - 2018/09/20/ AB - Therapeutic strategies that augment antiviral immunity and reduce the viral reservoir are critical to achieving durable remission of HIV. The coinhibitory receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during chronic HIV and SIV infections. We previously demonstrated that in vivo blockade of PD-1 during chronic SIV infection improves the function of antiviral CD8+ T cells and B cells. Here, we tested the immunological and virological effects of PD-1 blockade combined with antiretroviral therapy (ART) in rhesus macaques. Administration of anti–PD-1 antibody 10 days prior to ART initiation rapidly enhanced antiviral CD8+ T cell function and diminished IFN-stimulated genes. This resulted in faster viral suppression in plasma and better Th17 cell reconstitution in the rectal mucosa following ART initiation. PD-1 blockade during ART resulted in lower levels of cell-associated replication-competent virus. Following ART interruption, PD-1 antibody–treated animals showed markedly higher expansion of proliferating CXCR5+perforin+granzyme B+ effector CD8+ T cells and lower regulatory T cells that resulted in better control of viremia. Our results show that PD-1 blockade can be administered safely with ART to augment antiviral CD8+ T cell function and reduce the viral reservoir, leading to improved control of viral rebound after ART interruption. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.122940 VL - 3 IS - 18 UR - https://doi.org/10.1172/jci.insight.122940 PB - The American Society for Clinical Investigation ER -