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

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


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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • CD8-Positive T-Lymphocytes
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Male
  • Middle Aged


  • Anti-Retroviral Agents
  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human

Associated data