Su Junwei, Zhang Junjie, Wang Qianying, Liu Xiaojing, Wang Shuo, Ruan Yuhua, Li Dan
The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Pathogens. 2025 Apr 4;14(4):347. doi: 10.3390/pathogens14040347.
The rapid initiation of highly active anti-retroviral therapy (HAART) can control HIV-1 viremia and stabilize the long-term health of people living with HIV-1 (PLWH). Despite this, individuals who are diagnosed late and exhibit poor therapeutic efficacy still pose a great challenge to global HIV management. To address this, we conducted comprehensive multiparametric immune profiling and analyzed its association with disease progression and therapeutic efficacy. Multicolor flow cytometry was used to characterize the circulating immune cell composition and cellular phenotypes in 40 treatment-naive individuals (16 chronic, 24 newly diagnosed), 26 HAART-treated individuals, and 18 healthy controls. Comparative analyses of T cell subsets, immune activation markers, and viral load signatures were performed, followed by network construction. We carried out principal component analysis and displayed the data by dimensionality reduction. Persistent immune activation, dysregulated regulatory immunity, and aberrant memory differentiation markers were identified in T cells of HIV-1-infected individuals and were associated with disease progression. Additionally, HAART-treated patients which did not fully restore CD4 T cells exhibited higher levels of activated markers, suggesting possible biomarkers of therapeutic efficacy. This study describes changes in immune cell profiles throughout HIV-1 disease progression and explores suitable laboratory predictors for future clinical and therapeutic settings by monitoring pathological immune cell events.
高效抗逆转录病毒疗法（HAART）的迅速启动能够控制HIV-1病毒血症，并稳定HIV-1感染者（PLWH）的长期健康状况。尽管如此，诊断较晚且治疗效果不佳的个体仍然给全球HIV管理带来巨大挑战。为解决这一问题，我们进行了全面的多参数免疫分析，并分析了其与疾病进展和治疗效果的关联。采用多色流式细胞术对40名未经治疗的个体（16名慢性感染者、24名新诊断感染者）、26名接受HAART治疗的个体以及18名健康对照者的循环免疫细胞组成和细胞表型进行表征。对T细胞亚群、免疫激活标志物和病毒载量特征进行比较分析，随后构建网络。我们进行了主成分分析，并通过降维展示数据。在HIV-1感染者的T细胞中鉴定出持续的免疫激活、失调的调节性免疫和异常的记忆分化标志物，这些与疾病进展相关。此外，未完全恢复CD4 T细胞的HAART治疗患者表现出更高水平的激活标志物，提示可能是治疗效果的生物标志物。本研究描述了HIV-1疾病进展过程中免疫细胞谱的变化，并通过监测病理性免疫细胞事件探索适用于未来临床和治疗环境的实验室预测指标。
