Gay Cynthia L, Bosch Ronald J, Ritz Justin, Hataye Jason M, Aga Evgenia, Tressler Randall L, Mason Stephen W, Hwang Carey K, Grasela Dennis M, Ray Neelanjana, Cyktor Josh C, Coffin John M, Acosta Edward P, Koup Richard A, Mellors John W, Eron Joseph J
Department of Medicine, University of North Carolina at Chapel Hill.
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
J Infect Dis. 2017 Jun 1;215(11):1725-1733. doi: 10.1093/infdis/jix191.
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.
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.
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.
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.
NCT02028403.
使用抗程序性死亡受体配体1（PD-L1）抗体逆转免疫耗竭可能会改善1型人类免疫缺陷病毒（HIV-1）特异性免疫，并增加表达HIV-1的细胞的清除率。
我们开展了一项关于BMS-936559的I期随机双盲安慰剂对照剂量递增研究，研究对象为年龄在18岁以上至70岁以下、接受抑制性抗逆转录病毒治疗、CD4+细胞计数>350个/μL且通过单拷贝检测可检测到血浆HIV-1 RNA的HIV-1感染成人。描述了单次输注BMS-936559（0.3mg/kg）与安慰剂的数据。主要结局为安全性，定义为任何3级或更高级别的或免疫相关不良事件（AE），以及从基线到输注后第28天HIV-1 gag特异性CD8+T细胞反应的变化。
8名男性入组：6名接受0.3mg/kg的BMS-936559，2名接受安慰剂输注。没有与BMS-936559相关的3级或更高级别的AE。在1名参与者中，在输注BMS-936559后266天发现无症状垂体炎（一种方案定义的免疫相关AE）；它随时间消退。表达干扰素γ的HIV-1 gag特异性CD8+T细胞的平均百分比从基线时的（0.09%）增加到第28天的（0.20%；P = 0.14），这是由2名接受BMS-936559的参与者的大幅增加所驱动的。
在首次对健康的HIV-1感染者进行免疫检查点抑制剂评估中，单次低剂量输注BMS-936559似乎在一部分参与者中增强了HIV-1特异性免疫。
NCT02028403。
