Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy

CL Gay, RJ Bosch, J Ritz, JM Hataye… - The Journal of …, 2017 - academic.oup.com
CL Gay, RJ Bosch, J Ritz, JM Hataye, E Aga, RL Tressler, SW Mason, CK Hwang…
The Journal of infectious diseases, 2017academic.oup.com
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 …
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.
Oxford University Press