cART effects on glial cells

联合抗逆转录病毒疗法(CART)被认为是极大地抑制了 艾滋病大流行，越来越多地被用作预防艾滋病毒的预防性治疗 在“高危”人群中传播。尽管取得了这些治疗进展，但艾滋病毒感染 与许多共同疾病有关，其中最值得注意的是一系列 神经认知障碍称为HIV相关性神经退行性疾病(HAND)。这个 艾滋病毒对手头购物车的贡献尚不清楚。独立于艾滋病毒的CART可能会产生负面影响 中枢神经系统(CNS)的冲击细胞。虽然一些研究表明直接 CART的神经毒性作用，对其对巨微胶质细胞的影响知之甚少。 星形胶质细胞和小胶质细胞/巨噬细胞)。神经胶质细胞协调免疫 与神经元和内皮细胞的反应和交流。神经胶质细胞的失调 与包括手部在内的许多神经退行性疾病有关。在此应用程序中，在 目的1我们将确定CART(Atripla和Triumeq)对表型和 星形胶质细胞、小胶质细胞和单核细胞来源的巨噬细胞的功能。 在目标2中，我们将在体内确定CART对神经胶质细胞和神经炎症的影响 人性化的老鼠。总而言之，这些研究将揭示CART对神经胶质细胞和其 对神经元健康和血脑屏障完整性的后续影响以及信息 联合应用抗逆转录病毒药物将保持最小中枢神经系统的治疗效果 监管失调。

Combination antiretroviral therapy (cART) is appropriately credited with dramatically curbing the AIDS pandemic and is increasingly being used as a prophylactic treatment to prevent HIV transmission among “at high-risk” populations. Despite these therapeutic advances, HIV infection is associated with a number of co-morbid conditions, the most notable of which is a spectrum of neurocognitive disorders termed HIV Associated Neurodegenerative Disorders (HAND). The contribution of HIV vs. cART on HAND is not clear. cART, independent of HIV, may negatively impact cells of the Central Nervous System (CNS). While some studies demonstrated direct neurotoxic effects of cART, little is known about their impact on macro and micro glial cells (e.g. astrocytes and microglia/macrophages, respectively). Glial cells coordinate immunologic responses and communication with neurons and endothelial cells. Dysregulation of glial cells is associated with a number of neurodegenerative diseases, including HAND. In this application, in Aim 1 we will determine the impact of cART (Atripla and Triumeq) on the phenotype and function of astrocytes, microglia, and monocyte- derived macrophages (MDMs). In Aim 2, we will determine the impact of cART on glia and neuroinflammation in vivo humanized mice. Collectively, these studies will reveal the impact of cART on glial cells and its subsequent effects on neuronal health and blood brain barrier integrity as well as inform combination of antiretrovirals that will retain therapeutic efficacy with minimal CNS dysregulation.