학술논문
Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy
Document Type
Clinical report
Author
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
Source
Open Forum Infectious Diseases. March, 2024, Vol. 11 Issue 3
Subject
Language
English
ISSN
2328-8957
Abstract
Background. T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific [CD4.sup.+] 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.sup.+] counts [greater than or equal to] 350 cells/[micro]L 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.sup.+] and [CD8.sup.+] T-cell responses were evaluated. Results. Five men were enrolled (median [CD4.sup.+] count, 911 cells/[micro]L; 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.sup.+] 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. Keywords. anti-PD-1 inhibitor; HIV; HIV cure; HIV latency; immune checkpoint inhibitors.
Immune checkpoint therapy (ICT) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]) has revolutionized immunotherapy for cancer [1] and is standard of care for several malignancies. [...]
Immune checkpoint therapy (ICT) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]) has revolutionized immunotherapy for cancer [1] and is standard of care for several malignancies. [...]