Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy

作者：Cynthia L. Gay, Ronald J. Bosch, Ashley McKhann, Raymond Cha, Gene D. Morse, Chanelle Wimbish, Danielle Campbell, Kendall F. Moseley, Steven Hendrickx, Michael Messer, Constance A. Benson, Edgar T. Overton, Anne Paccaly, Vladimir Janković, Elizabeth Miller, Randall Tressler, Jonathan Z. Li, Daniel R. Kuritzkes, Bernard Macatangay, Joseph J. Eron, William D. Hardy, for the A5370 Team, Amanda Tipton, Susan Pedersen, Bernadette Jarocki, Scott T. Anderson, Lynette Purdue, Kyle Whitson, Sara Zabih, Cheryl Jennings, Pamela Lankford-Turner, Patrick Mehta, Thomas S. Uldrick · 发表于：Open Forum Infectious Diseases · 年份：2024 · DOI：10.1093/ofid/ofad694 · 被引用次数：15 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers

Abstract Background T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4+ T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir. Methods This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4+ counts ≥350 cells/μL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE). Changes in HIV-1–specific polyfunctional CD4+ and CD8+ T-cell responses were evaluated. Results Five men were enrolled (median CD4+ count, 911 cells/μL; median age, 51 years); 2 received 1 dose of cemiplimab, 2 received 2 doses, and 1 received placebo. One participant had a probable irAE (thyroiditis, grade 2); another had a possible irAE (hepatitis, grade 3), both after a single low-dose (0.3 mg/kg) infusion. The Safety Monitoring Committee recommended no further enrollment or infusions. All 4 cemiplimab recipients were followed for 48 weeks. No other cemiplimab-related serious AEs, irAEs, or grade 3 or higher AEs occurred. One 2-dose recipient of cemiplimab had a 6.2-fold increase in polyfunctional, Gag-specific CD8+ T-cell frequency with supportive increases in plasma HIV RNA and decreases in total HIV DNA. Conclusions One of 4 participants exhibi...