The Journal of infectious diseases 2017 04 18() doi 10.1093/infdis/jix191
Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells.
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.
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.
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.