Ji Jiahao, Guo Caiping, Li Zhen, Cai Miaotian, Wang Rui, Chen Xue, Zhang Yulin, Wu Hao, Zhang Tong, Zhang Yang
Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
Beijing Institute of Sexually Transmitted Disease Prevention and Control, Beijing, 100069, People's Republic of China.
Infect Drug Resist. 2025 Jul 9;18:3427-3437. doi: 10.2147/IDR.S522910. eCollection 2025.
Initiating antiretroviral therapy promptly (rapid ART) is linked to better immune recovery in people with HIV (PWH), although its specific effects on immune dysregulation remain partially understood. We have discovered a "pathological proliferation" phenomenon, marked by T cell over-proliferation and exhaustion in PWH, potentially hindering full immune recovery. The objective of this research is to examine how rapid ART affects T-cell pathological proliferation, immune recovery, and systemic inflammation in PWH.
In this cross-sectional study (conducted at Beijing Youan Hospital, Capital Medical University, China, from April 1 to September 18, 2022), we recruited 39 PWH, including 23 in the rapid ART group (within 30 days) and 16 in the non-rapid ART group (after 180 days). Fasting venous blood samples were collected in the morning. Immune phenotypes of T cells were analyzed using mass cytometry and Luminex.
The rapid ART group demonstrated a significant decline in Ki67⁺ CD4⁺ and CD8⁺ T cells. Within this group, a higher percentage of naive T (T) cells was observed in CD4⁺ T cells, along with a remarkable reduction in Ki67 expression. Additionally, CD8⁺ T cells in the rapid ART group exhibited an increased presence of T cells while showing a decreased proportion of PD-1/HLA-DR/CD38 high-expressing cells. In addition, the rapid ART group exhibited significantly lower IL-18 levels. T cells (CD31 HLA-DR CD38 CD57 PD-1) and central memory T (T) cells (HLA-DR CD38 PD-1 CD57) that were not suppressed by rapid ART showed significant correlations with baseline CD4 counts, HIV loads, and recent CD4/CD8 ratio.
These findings suggest rapid ART may curb pathological T cell proliferation and improved immune recovery in PWH. Despite these benefits, persistent immune activation in some individuals highlights the need for targeted immune monitoring and potential adjunctive interventions to optimize long-term immune health in PWH.
及时启动抗逆转录病毒治疗（快速抗逆转录病毒治疗）与人类免疫缺陷病毒感染者（PWH）更好的免疫恢复相关，尽管其对免疫失调的具体影响仍部分未知。我们发现了一种“病理性增殖”现象，其特征为PWH中T细胞过度增殖和耗竭，这可能会阻碍完全免疫恢复。本研究的目的是探讨快速抗逆转录病毒治疗如何影响PWH中T细胞的病理性增殖、免疫恢复和全身炎症。
在这项横断面研究中（于2022年4月1日至9月18日在中国首都医科大学附属北京佑安医院进行），我们招募了39名PWH，其中23名在快速抗逆转录病毒治疗组（30天内），16名在非快速抗逆转录病毒治疗组（180天后）。于早晨采集空腹静脉血样本。使用质谱流式细胞术和Luminex分析T细胞的免疫表型。
快速抗逆转录病毒治疗组中Ki67⁺ CD4⁺和CD8⁺ T细胞显著减少。在该组中，CD4⁺ T细胞中幼稚T（T）细胞的百分比更高，同时Ki67表达显著降低。此外，快速抗逆转录病毒治疗组中的CD8⁺ T细胞显示T细胞数量增加，而PD-1/HLA-DR/CD38高表达细胞的比例降低。此外，快速抗逆转录病毒治疗组的IL-18水平显著更低。未被快速抗逆转录病毒治疗抑制的T细胞（CD31 HLA-DR CD38 CD57 PD-1）和中枢记忆T（T）细胞（HLA-DR CD38 PD-1 CD57）与基线CD4计数、HIV载量和近期CD4/CD8比值显著相关。
这些发现表明快速抗逆转录病毒治疗可能抑制PWH中病理性T细胞增殖并改善免疫恢复。尽管有这些益处，但一些个体中持续的免疫激活凸显了对PWH进行有针对性的免疫监测和潜在辅助干预以优化长期免疫健康的必要性。
