Xu Yinyan, Trumble Ilana M, Warren Joanna A, Clutton Genevieve, Abad-Fernandez Maria, Kirchnerr Jennifer, Adimora Adaora A, Deeks Steven G, Margolis David M, Kuruc JoAnn D, Gay Cynthia L, Archin Nancie M, Mollan Katie R, Hudgens Michael, Goonetilleke Nilu
Department of Microbiology & Immunology, UNC Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Department of Biostatistics, UNC Chapel Hill, Chapel Hill, NC 27516, USA.
Mol Ther Methods Clin Dev. 2019 Aug 14;15:9-17. doi: 10.1016/j.omtm.2019.07.008. eCollection 2019 Dec 13.
HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/10 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6-12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV.
HIV感染会引发强烈的T细胞反应,这种反应由高病毒血症维持,但在抗逆转录病毒疗法(ART)开始后会下降。关于接受长期治疗的个体中HIV特异性T细胞反应的后续稳定性,报道相对较少。这些数据对于为基于T细胞的免疫疗法的临床试验提供支持至关重要。在一项横断面研究中,尽管接受ART的中位数持续抑制时间为5.0年,但通过干扰素(IFN)-γ ELISpot检测,HIV感染者(PLWH;n = 34)中可检测到HIV特异性T细胞反应(平均约1,100个斑点形成单位[SFUs]/10个外周血单个核细胞)。未检测到总和的HIV特异性T细胞反应与有复制能力的HIV储存库大小之间存在实质性关联。接下来,对每周、每月或每年采样的参与者进行T细胞反应测量。在检查的时间段内,HIV特异性T细胞反应高度稳定;个体内变异范围从每周采样的16%变异系数(CV)到每年采样的27% CV。这些数据用于为未来的免疫疗法研究进行功效计算。在接受抑制性治疗的PLWH中,HIV特异性T细胞反应的稳定性将使小规模(例如,n = 6 - 12)的有功效研究成为可能,便于对基于T细胞的HIV免疫疗法进行快速和迭代测试。