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

• Published in: Open forum infectious diseases Vol. 11; no. 3; p. ofad694
• Main Authors: Gay, Cynthia L, Bosch, Ronald J, McKhann, Ashley, Cha, Raymond, Morse, Gene D, Wimbish, Chanelle L, Campbell, Danielle M, Moseley, Kendall F, Hendrickx, Steven, Messer, Michael, Benson, Constance A, Overton, Edgar T, Paccaly, Anne, Jankovic, Vladimir, Miller, Elizabeth, Tressler, Randall, Li, Jonathan Z, Kuritzkes, Daniel R, Macatangay, Bernard J C, Eron, Joseph J, Hardy, W David
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-03-2024
• Subjects: Clinical Trials and Therapeutics; anti-PD-1 inhibitor; immune checkpoint inhibitors; HIV; HIV latency; HIV cure
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofad694

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 exhibited increased HIV-1-specific T-cell responses and transiently increased HIV-1 expression following 2 cemiplimab infusions. The occurrence of irAEs after a single, low dose may limit translating the promising therapeutic results of cemiplimab for cancer to immunotherapeutic and latency reversal strategies for HIV.
Clinical Trials Registration.
NCT03787095.
One of 4 participants administered anti-PD-1 antibody exhibited increased HIV-1–specific T-cell responses and transiently increased HIV-1 expression. Significant immune-related adverse events after a single, low dose of anti-PD-1 antibody may limit translating the benefits of anti-PD-1 therapies from cancer to HIV.