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
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DOI：
10.1093/infdis/jix191
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发表时间：
2017-06-01
影响因子：
6.4
通讯作者：
Eron, Joseph J.
中科院分区：
文献类型：
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作者：
Gay, Cynthia L.;Bosch, Ronald J.;Eron, Joseph J.
背景资料。使用抗PD-L1抗体逆转免疫衰竭，可提高人类免疫缺陷病毒1型(HIV-1)的特异性免疫，增加表达HIV-1的细胞的清除。我们进行了BMS-936559的I期随机、双盲、安慰剂对照、剂量递增研究，包括年龄为18岁至350个细胞/亩的L和可检测到血浆HIV-1RNA的成人。关于单次输注bms-936559(0.3 mg/kg)与安慰剂的数据进行了描述。主要结果是安全性定义为任何3级或更高级别或与免疫相关的不良事件(AE)，以及从基线到注射后第28天HIV-1 Gag特异性CD8(+)T细胞反应的变化。8名男性入选：6名接受了0.3毫克/公斤的BMS-936559，2名接受了安慰剂注射。没有与BMS-936559相关的3级或更高级别的AEs。在1名参与者中，在注射BMS-936559后第266天发现无症状脑垂体炎(一种方案定义的免疫相关AE)；它随着时间的推移而消失。表达干扰素的HIV-1 Gag特异性CD8(+)T细胞的平均百分比。从基线(0.09%)到第28天(0.20%；P=0.14)增加，这是由2名接受BMS-936559的参与者大幅增加推动的。在对健康的艾滋病毒-1感染者的免疫检查点抑制剂的首次评估中，单一低剂量的bms-936559输注似乎增强了一部分参与者的艾滋病毒-1特异性免疫力。
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 = 350 cells/mu L 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. 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.