Advertisement

 

 

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

Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.
Author Information (click to view)

Gay 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, ,


Gay 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, , (click to view)

Gay 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, ,

Advertisement

The Journal of infectious diseases 2017 04 18() doi 10.1093/infdis/jix191

Abstract
Background.
Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells.

Methods.
Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥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 immune-related adverse event (AE) and the change in HIV-1 Gag-specific CD8+ T cells responses from baseline to day 28 post-infusion.

Results.
Eight men enrolled; six received 0.3 mg/kg of BMS-936559 and two received placebo infusions. There were no BMS-936559 related >Grade 3 AEs. In one participant, asymptomatic hypophysitis (a protocol-defined immune-related AE) was identified 266 days following BMS-936559 infusion that resolved over time. The mean percentage of HIV-1 Gag-specific CD8+ T cells expressing IFN-γ increased from baseline (0.09%) through day 28 (0.20%; p=0.14), driven by substantial increases in two participants who received BMS-936559.

Discussion.
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

five × two =

[ HIDE/SHOW ]