Compartmentalized CSF viral escape and the CNS HIV reservoir

摘要 脑脊髓液（CSF）HIV逃逸是指中枢神经系统疾病的严重程度 系统（CNS）HIV感染，反映在CSF HIV RNA浓度中，等于或超过HIV RNA浓度 在抗逆转录病毒治疗（ART）期间在血液中测量的浓度。三种类型的脑脊液逃逸已经 确定：神经症状性，其中有明确的CNS损伤临床证据，无症状性， 记录的损伤，以及由非HIV CNS感染引起的继发性。每一个都是在一个环境中发展起来的 其中ART对CNS的影响小于系统性HIV感染，从而允许详细检查 相对“孤立”的CNS病毒群。这一补充建议扩展了我们正在进行的研究项目， 两种方式。Specific Aim S1为分子病毒学分析引入了两种罕见且宝贵的样品集， 定义神经症状性和继发性CSF逃逸中CSF HIV人群的起源。具体目标S2 支持使用新技术测量大量CSF和血液生物标志物，以更好地表征 所有三种类型的CSF逃逸的炎症和神经学特征。总的来说，这些补充 研究将促进我们对系统性和中枢神经系统HIV感染之间交换的理解，包括 从中枢神经系统艾滋病病毒库和持续的播种从血液的贡献。这种理解将 促进对艾滋病毒治疗后这些不寻常方面的临床识别、诊断和管理， 为CNS HIV感染的起源、发病机制和治疗提供了更广泛的见解。

Abstract Cerebrospinal fluid (CSF) HIV escape refers to clinical settings in which the magnitude of central nervous system (CNS) HIV infection, reflected in the CSF HIV RNA concentration, is equal to or exceeds the HIV RNA concentration measured in blood during antiretroviral therapy (ART). Three types of CSF escape have been identified: Neurosymptomatic, in which there is clear clinical evidence of CNS injury, Asymptomatic without documented injury, and Secondary provoked by a non-HIV CNS infection. Each of these develops in a setting where ART exerts less effect on CNS than systemic HIV infection, thereby permitting detailed examination of a relatively ‘isolated’ CNS viral population. This Supplemental proposal extends our ongoing research project in two ways. Specific Aim S1 introduces two rare and invaluable sample sets for molecular virological analysis to define the origins of CSF HIV populations in Neurosymptomatic and Secondary CSF Escape. Specific Aim S2 supports use of novel technology to measure a large array of CSF and blood biomarkers to better characterize the inflammatory and neurological features of all three types of CSF escape. Overall, these Supplementary studies will advance our understanding of the exchange between systemic and CNS HIV infection, including the contributions to from a CNS HIV reservoir and ongoing seeding from the blood. This understanding will advance the clinical recognition, diagnosis and management of these unusual aspects of treated HIV, and provide broader insights into the origins, pathogenesis and treatment of CNS HIV infections.