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

TitleClinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2017
AuthorsGay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, Mason SW, Hwang CK, Grasela DM, Ray N, Cyktor JC, Coffin JM, Acosta EP, Koup RA, Mellors JW, Eron JJ
Corporate AuthorsAIDS Clinical Trials 5326 Study Team
JournalJ Infect Dis
Date Published2017 Jun 01
KeywordsAdult, Anti-Retroviral Agents, Antibodies, Monoclonal, B7-H1 Antigen, CD8-Positive T-Lymphocytes, HIV Infections, HIV-1, Humans, Male, Middle Aged

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.

Alternate JournalJ. Infect. Dis.
PubMed ID28431010
PubMed Central IDPMC5790148
Grant ListUM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States