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J Infect Dis. 2017 Jun 1;215(11):1725-1733. doi: 10.1093/infdis/jix191.

Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.

Author information

1
Department of Medicine, University of North Carolina at Chapel Hill.
2
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
3
Immunology Laboratory, Vaccine Research Center.
4
Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
5
Columbus Technologies, El Segundo, California.
6
Bristol-Myers Squibb, Wallingford, Connecticut.
7
Bristol-Myers Squibb, Princeton, New Jersey.
8
Department of Medicine, University of Pittsburgh, Pennsylvania.
9
Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts.
10
Department of Pharmacology and Toxicology, University of Alabama School of Medicine, Birmingham.

Abstract

Background:

Reversing immune exhaustion with an anti-PD-L1 antibody may improve human immunodeficiency virus type 1 (HIV-1)-specific immunity and increase clearance of HIV-1-expressing cells.

Methods:

We conducted a phase I, randomized, double-blind, placebo-controlled, dose-escalating study of BMS-936559, including HIV-1-infected adults aged >18 to <70 years on suppressive antiretroviral therapy with CD4+ counts >350 cells/μL and detectable plasma HIV-1 RNA by single-copy assay. Data on single infusions of BMS-936559 (0.3 mg/kg) versus placebo are described. The primary outcomes were safety defined as any grade 3 or greater or immune-related adverse event (AE) and the change in HIV-1 Gag-specific CD8+ T cell responses from baseline to day 28 after infusion.

Results:

Eight men enrolled: 6 received 0.3 mg/kg of BMS-936559, and 2 received placebo infusions. There were no BMS-936559-related grade 3 or greater AEs. In 1 participant, asymptomatic hypophysitis (a protocol-defined immune-related AE) was identified 266 days after BMS-936559 infusion; it resolved over time. The mean percentage of HIV-1 Gag-specific CD8+ T cells expressing interferon γ increased from baseline (0.09%) through day 28 (0.20%; P = .14), driven by substantial increases in 2 participants who received BMS-936559.

Conclusions:

In this first evaluation of an immunologic checkpoint inhibitor in healthy HIV-1-infected persons, single low-dose BMS-936559 infusions appeared to enhance HIV-1-specific immunity in a subset of participants.

Clinical Trials Registration:

NCT02028403.

KEYWORDS:

BMS-936559; HIV cure; HIV eradication; anti-PD-L1; checkpoint inhibitors; human immunodeficiency virus type 1 (HIV-1); immune response

PMID:
28431010
PMCID:
PMC5790148
DOI:
10.1093/infdis/jix191
[Indexed for MEDLINE]
Free PMC Article

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