U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland.
AIDS. 2020 Feb 1;34(2):197-202. doi: 10.1097/QAD.0000000000002432.
Activated (CD38HLA-DR) PD-1 CD4 T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4 T-cell populations to measure relative contributions to viral reservoirs.
Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4 T-cell populations and their contribution to viral reservoirs.
We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4 T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform.
Concomitant with viral load decline and CD4 T-cell count rebound, the activated PD-1 CD4 T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1 CD4 T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1 CD4 T cells was associated with poorer CD4 T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover.
Activated PD-1 CD4 T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.
在未经治疗的 HIV-1 感染和接受 ART 个体中病毒持续存在的情况下，活化（CD38+HLA-DR）PD-1 CD4 T 细胞与病毒复制和疾病进展密切相关。很少有研究检测过不同活化 CD4 T 细胞群中的细胞相关病毒载量（CAVL），以衡量其对病毒储存库的相对贡献。
对开始接受 ART 的乌干达慢性 HIV-1 感染者进行纵向评估，以研究活化 CD4 T 细胞群及其对病毒储存库的贡献。
我们对来自乌干达坎帕拉的 32 名慢性 HIV-1 感染者进行了随访，并在开始 ART 后的基线、6 个月和 12 个月时测定了他们的 CD4 T 细胞计数和病毒载量。根据激活谱对 T 细胞群进行分类，并测量 gag DNA 以确定这些群体中的 CAVL。使用多重平台在血浆中测量与炎症相关的可溶性因子。
在病毒载量下降和 CD4 T 细胞计数反弹的同时，活化的 PD-1 CD4 T 细胞群在开始接受 ART 时收缩。活化的 PD-1 CD4 T 细胞的基线水平与血浆中 IP-10 和 TNFRII 的水平相关。有趣的是，较高的基线水平的活化的 PD-1 CD4 T 细胞与 12 个月 ART 后 CD4 T 细胞恢复较差相关。该群体在基线时对细胞相关 HIV DNA 载量有显著贡献，而在接受 ART 后其贡献下降，表明其高周转率。
活化的 PD-1 CD4 T 细胞是 ART 免疫恢复不良的预测因子，可能代表 HIV-1 储存库中的一个短暂组成部分。
