> Details

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; Tipton, Amanda; Pedersen, Susan; Jarocki, Bernadette; [...]

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

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  • Media type: E-Article
  • Title: Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy
  • Contributor: 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; Tipton, Amanda; Pedersen, Susan; Jarocki, Bernadette; [...]
  • imprint: Oxford University Press (OUP), 2024
  • Published in: Open Forum Infectious Diseases
  • Language: English
  • DOI: 10.1093/ofid/ofad694
  • ISSN: 2328-8957
  • Keywords: Infectious Diseases ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> <jats:p>Clinical Trials Registration. NCT03787095.</jats:p> </jats:sec>
  • Access State: Open Access