Pathology Advanced Translational Research Unit (PATRU), Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Emory Vaccine Center, Atlanta, GA, USA.
Nat Immunol. 2024 Oct;25(10):1900-1912. doi: 10.1038/s41590-024-01952-4. Epub 2024 Sep 12.
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8 T cells in lymph nodes and reduced expression of BCL-2 in CD4 T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4 and CD8 T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.
人类免疫缺陷病毒（HIV）在抗逆转录病毒治疗（ART）期间的持续存在与血浆白细胞介素-10（IL-10）水平升高和 PD-1 表达有关。我们假设 IL-10 和 PD-1 阻断将导致分析性治疗中断（ATI）后病毒反弹得到控制。28 只接受 ART 治疗、感染猴免疫缺陷病毒（SIV）的恒河猴（RMs）接受了抗 IL-10、抗 IL-10 加抗 PD-1（组合）或载体治疗。免疫治疗引入 12 周后，ART 被中断。在 ATI 后 >24 周的时间里，10 只组合治疗的 RMs 中有 9 只观察到病毒反弹的持续控制。ATI 前诱导炎症细胞因子、淋巴结中效应性 CD8 T 细胞的增殖以及 CD4 T 细胞中 BCL-2 的表达降低，预测了病毒反弹的控制。ATI 后 24 周，较低的病毒载量与组合治疗的 RMs 血液和淋巴结中表达 TCF-1 的记忆 T 细胞以及 SIV 特异性 CD4 和 CD8 T 细胞的频率较高相关。这些结果为实现 ART 停药后 HIV 和/或 SIV 的长期控制指明了道路。
