Long-Term CNS Consequences of Treatment During Acute Infection

描述（由申请方提供）：急性HIV期间发生的全身免疫反应和中枢神经系统（CNS）事件可能为慢性HIV相关CNS损伤和CNS相关HIV储库的建立奠定了基础。正如最早期的系统特征，如血浆HIV RNA峰值、T细胞活化水平和CD 4细胞早期丢失是HIV疾病轨迹的关键决定因素一样，在最早期阶段启动的CNS过程可能对CNS相关病毒储库的建立、CNS区室化病毒、宿主控制CNS病毒的能力以及感染的长期CNS后果提供重要信息。逻辑上的挑战导致严重依赖动物数据来定义急性HIV期间可能的CNS事件。在本申请中，我们扩展了与美国陆军在泰国进行的研究的现有合作伙伴关系，以确定这些人类最早的事件，并确定影响长期CNS结果的因素。本申请拟为在急性HIV期间（暴露后< 1个月）入组的60名泰国受试者提供密集的CNS表征。在我们的方案中，一半的受试者将在初步评估后立即开始HAART，为期18个月。我们将纵向表征CNS临床事件、神经学、神经心理学和精神病学因素、多模式磁共振成像、CSF免疫学和隔室特异性全基因组HIV测序，以确定急性HIV中发生的事件如何影响慢性HIV CNS疾病。我们还将确定CNS创始人和已建立的病毒，并确定早期HAART干预是否会影响这些关系。母研究包括广泛的全身免疫学和病毒学特征，使我们能够确定最早的全身性事件是否影响长期CNS结局。

DESCRIPTION (provided by applicant): The systemic immune response and central nervous system (CNS) events occurring during acute HIV likely set the stage for chronic HIV-related CNS injury and the establishment of CNS-relevant HIV reservoirs. Just as the earliest systemic features such as peak plasma HIV RNA, level of T-cell activation, and early loss of CD4 cells are crucial determinants of HIV disease trajectory, CNS processes initiated during the earliest stages may critically inform the establishment of a CNS-relevant viral reservoirs, CNS compartmentalized virus, the hosts' ability to control CNS virus, and the long-term CNS consequences of infection. Logistical challenges have lead to heavy reliance on animal data to define the likely CNS events during acute HIV. In this application, we extend existing partnerships with US Army studies underway in Thailand to define these earliest events in humans and determine factors that influence long-term CNS outcomes. This application proposes to provide intensive CNS characterization for 60 Thai subjects enrolled during acute HIV (< 1 month after exposure). In our schema, one-half of subjects will begin HAART immediately after initial assessments for a fixed 18-month course. We will longitudinally characterize CNS clinical events, neurological, neuropsychological, and psychiatric factors, multimodal magnetic resonance imaging, CSF immunology and compartment specific full-genome HIV sequencing to determine how the events that occur in acute HIV impact chronic HIV CNS disorders. We will also determine CNS founder and established viruses and determine if early HAART intervention impacts these relationships. The parent studies include extensive systemic immunological and virological characterization allowing us to determine if the earliest systemic events impact long-term CNS outcomes.