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

Author:

Gay Cynthia L1ORCID,Bosch Ronald J2ORCID,McKhann Ashley2,Cha Raymond3ORCID,Morse Gene D3ORCID,Wimbish Chanelle L4,Campbell Danielle M5,Moseley Kendall F6ORCID,Hendrickx Steven7,Messer Michael8ORCID,Benson Constance A7ORCID,Overton Edgar T89ORCID,Paccaly Anne10ORCID,Jankovic Vladimir10ORCID,Miller Elizabeth10,Tressler Randall11,Li Jonathan Z12,Kuritzkes Daniel R12ORCID,Macatangay Bernard J C13ORCID,Eron Joseph J1ORCID,Hardy W David14ORCID, ,Tipton Amanda,Pedersen Susan,Jarocki Bernadette,Anderson Scott,Purdue Lynette,Whitson Kyle,Zabih Sara,Jennings Cheryl,Lankford-Turner Pamela,Mehta Patrick,Uldrick Thomas

Affiliation:

1. Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA

2. Department of Biostatistics, Center for Biostatistics and AIDS Research, Harvard T. H. Chan School of Public Health, Boston , Massachusetts , USA

3. Center for Integrated Global Biomedical Sciences, University at Buffalo , Buffalo, New York , USA

4. Department of Clinical Research, Social and Scientific Systems, Inc, a DLH Company , Silver Spring, Maryland , USA

5. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California , USA

6. Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA

7. Department of Medicine, University of California, San Diego , San Diego, California , USA

8. Department of Medicine, University of Alabama at Birmingham , Birmingham, Alabama , USA

9. North America Medical Affairs, ViiV Healthcare , Durham, North Carolina , USA

10. Departments of Clinical Sciences, Translational Medicine and Precision Medicine, Regeneron Pharmaceuticals, Inc , Tarrytown, New York , USA

11. HIV Research Branch, Division of AIDS, National Institute of AIDS, National Institutes of Health , Rockville, Maryland , USA

12. Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts , USA

13. Division of Infectious Diseases, University of Pittsburgh , Pittsburgh, Pennsylvania , USA

14. Division of Infectious Diseases, Keck School of Medicine, University of Southern California , Los Angeles, California , USA

Abstract

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.

Funder

National Institutes of Health

University of North Carolina at Chapel Hill Center for AIDS Research

National Center for Advancing Translational Sciences

Publisher

Oxford University Press (OUP)

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