Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons.
Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons.
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ART 中对 3BNC117 和 10-1074 的敏感性抑制了慢性感染者。
DOI：
10.1097/qad.0000000000003575
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Mounzer,Karam
中科院分区：
文献类型：
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作者：
Tebas,Pablo;Lynn,Kenn;Azzoni,Livio;Cocchella,Giorgio;Papasavvas,Emmanouil;Fair,Matthew;Karanam,Brijesh;Sharma,Paridhima;Reeves,JacquelineD;Petropoulos,ChristosJ;Lalley-Chareczko,Linden;Kostman,JayR;Short,William;Mounzer,Karam
目的：本研究的目的是评估艾滋病病毒的易感性，两个艾滋病病毒单克隆抗体（bnAbs），3BNC 117和10-1074，在个人与慢性抗逆转录病毒治疗（ART）抑制HIV infection.Design：的bnAbs的易感性测定使用的PhenoSense单克隆抗体检测，这是一种基于细胞的感染性试验，旨在评估的易感性的报告假病毒粒子。该检测是唯一的临床实验室改进修正案（CLIA）/美国病理学家学院（CAP）兼容的筛选测试，专门开发用于评估bnAb在人与HIV infection.Method的易感性：的敏感性的双链酶报告假病毒，来自HIV-1包膜蛋白从61 ART抑制个体的外周血单核细胞，3BNC 117和10-1074 bnAb使用PhenoSense单克隆抗体检测进行了评估。敏感性被定义为3BNC 117和10-1074的IC 90分别< 2.0 μg/ml和1.5 μg/ml。结果：约一半的慢性感染和病毒学抑制的个体被发现携带病毒，对一种或两种测试bnAbs.Conclusions：3BNC 117和10-1074的联合敏感性降低突出了仅使用两种bnAbs进行暴露前预防或治疗的潜在局限性。需要进一步的研究来定义和验证bnAb敏感性的临床相关性。
Objective:The aim of this study was to assess the susceptibility of HIV to two HIV monoclonal antibodies (bnAbs), 3BNC117 and 10-1074, in individuals with chronically antiretroviral therapy (ART) suppressed HIV infection.Design:The susceptibility of bnAbs was determined using the PhenoSense mAb Assay, which is a cell-based infectivity assay designed to assess the susceptibility of luciferase-reporter pseudovirions. This assay is the only Clinical Laboratory Improvement Ammendment (CLIA)/College of American Pathologist (CAP) compliant screening test specifically developed for evaluating bnAb susceptibility in people with HIV infection.Method:The susceptibility of luciferase-reporter pseudovirions, derived from HIV-1 envelope proteins obtained from peripheral bloodmononuclear cells of 61 ART-suppressed individuals, to 3BNC117 and 10-1074 bnAbs was assessed using the PhenoSense mAb assay. Susceptibility was defined as an IC 90 of< 2.0 μg/ml and 1.5 μg/ml for 3BNC117 and 10-1074, respectively.Results:About half of the individuals who were chronically infected and virologically suppressed were found to harbor virus with reduced susceptibility to one or both of the tested bnAbs.Conclusions:The reduced combined susceptibility of 3BNC117 and 10-1074 highlights a potential limitation of using only two bnAbs for pre-exposure prophylaxis or treatment. Further studies are needed to define and validate the clinical correlates of bnAb susceptibility.