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)mac₂₃₉-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.

抗逆转录病毒治疗 (ART) 期间人类免疫缺陷病毒 (HIV) 的持续存在与血浆白细胞介素 10 (IL-10) 水平和 PD-1 表达升高相关。我们假设 IL-10 和 PD-1 阻断将导致分析治疗中断 (ATI) 后病毒反弹的控制。 28 只经 ART 治疗、感染猿猴免疫缺陷病毒 (SIV)mac ₂₃₉的恒河猴 (RM) 接受抗 IL-10、抗 IL-10 加抗 PD-1（组合）或媒介物治疗。引入免疫疗法后 12 周中断 ART。在 ATI 后 >24 周内，十分之九的联合治疗 RM 观察到病毒反弹的持久控制。 ATI前炎症细胞因子的诱导、淋巴结中效应CD8 ⁺ T细胞的增殖以及CD4 ⁺ T细胞中BCL-2表达的减少预测了病毒反弹的控制。 ATI 后 24 周，较低的病毒载量与联合治疗 RM 的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 细胞的较高频率相关。这些结果为停止 ART 后实现 HIV 和/或 SIV 的长期控制提供了一条途径。