Combination antiretroviral therapy (cART) has greatly increased life expectancy for human immunodeficiency virus-1 (HIV-1)-infected patients. Even given the remarkable success of cART, the virus persists in many different cells and tissues. The presence of viral reservoirs represents a major obstacle to HIV-1 eradication. These viral reservoirs contain latently infected long-lived cells. The “Shock and Kill” therapeutic strategy aims to reactivate latently infected cells by latency reversing agents (LRAs) and kill these reactivated cells by strategies involving the host immune system. The brain is a natural anatomical reservoir for HIV-1 infection. Brain macrophages, including microglia and perivascular macrophages, display productive HIV-1 infection. A mathematical model was used to analyze the dynamics of latently and productively infected brain macrophages during viral infection and this mathematical model enabled prediction of the effects of LRAs applied to the “Shock and Kill” strategy in the brain. The model was calibrated using reported data from simian immunodeficiency virus (SIV) studies. Our model produces the overarching observation that effective cART can suppress productively infected brain macrophages but leaves a residual latent viral reservoir in brain macrophages. In addition, our model demonstrates that there exists a parameter regime wherein the “Shock and Kill” strategy can be safe and effective for SIV infection in the brain. The results indicate that the “Shock and Kill” strategy can restrict brain viral RNA burden associated with severe neuroinflammation and can lead to the eradication of the latent reservoir of brain macrophages.

联合抗逆转录病毒疗法 (cART) 大大延长了人类免疫缺陷病毒 1 (HIV-1) 感染患者的预期寿命。即使 cART 取得了显着的成功，该病毒仍然存在于许多不同的细胞和组织中。病毒库的存在是根除 HIV-1 的主要障碍。这些病毒库包含潜伏感染的长寿命细胞。“休克和杀死”治疗策略旨在通过潜伏逆转剂 (LRA) 重新激活潜伏感染的细胞，并通过涉及宿主免疫系统的策略杀死这些重新激活的细胞。大脑是 HIV-1 感染的天然解剖库。脑巨噬细胞，包括小胶质细胞和血管周围巨噬细胞，表现出生产性 HIV-1 感染。使用数学模型来分析病毒感染期间潜伏和有效感染的脑巨噬细胞的动态，该数学模型能够预测 LRA 对大脑中“休克和杀死”策略的影响。该模型使用来自猿猴免疫缺陷病毒 (SIV) 研究的报告数据进行校准。我们的模型产生了总体观察结果，即有效的 cART 可以抑制有效感染的脑巨噬细胞，但会在脑巨噬细胞中留下残留的潜伏病毒库。此外，我们的模型表明存在一个参数机制，其中“休克和杀死”策略对大脑中的 SIV 感染是安全有效的。