Compartmentalized CSF viral escape and the CNS HIV reservoir

摘要 脑脊液(CSF)HIV逃逸是指临床环境中中枢神经系统 系统(CNS)HIV感染，反映在脑脊液中HIV RNA浓度等于或超过HIV RNA 在抗逆转录病毒治疗(ART)期间测量血液中的浓度。有三种类型的脑脊液逃逸 确诊：有神经症状，有明确的中枢神经系统损伤的临床证据，无症状，无 有记录的伤害，以及由非艾滋病毒中枢神经系统感染引起的继发性损伤。其中的每一个都是在一个环境中发展起来的 与系统性艾滋病毒感染相比，ART对中枢神经系统的影响较小，从而允许对 相对“隔离”的中枢神经系统病毒种群。这项补充建议将我们正在进行的研究项目扩展到 两种方式。特定目标S1引入了两个稀有和宝贵的样本集用于分子病毒学分析 明确脑脊液HIV种群在神经症状性和继发性脑脊液逃逸中的来源。特定目标2 支持使用新技术测量大量脑脊液和血液生物标记物，以更好地表征 三种类型的脑脊液逃逸的炎症和神经学特征。总的来说，这些补充资料 研究将增进我们对系统性和中枢神经系统艾滋病毒感染之间的交流的理解，包括 对来自中枢神经系统艾滋病毒储存库和正在进行的血液播种的贡献。这一理解将 促进临床认识、诊断和处理已治疗的艾滋病毒的这些不寻常方面，以及 为CNS HIV感染的起源、发病机制和治疗提供更广泛的见解。

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.