Long-Term CNS Consequences of Treatment During Acute Infection

急性感染期间治疗的长期中枢神经系统后果

• 批准号: 8307295
• 负责人: SERENA S SPUDICH
• 金额: $ 63.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-26 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307295
• 关键词: Acute; Affect; Anti-Retroviral Agents; Area; Brain Injuries; CD4 Positive T Lymphocytes; CNS processing; Central Nervous System Diseases; Cerebrospinal Fluid; Chronic; Clinical; Cognition Disorders; Cognitive; Consequences of HIV; DNA; Data; Development; Disease; Encephalitis; Enrollment; Event; Failure; Funding; Genome; Grant; HIV; HIV Infections; Human; Image; Immune; Immune response; Immunity; Immunology; Individual; Infection; Inflammation; Inflammatory; Intervention; Lead; Life; Link; Macaca mulatta; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; National Institute of Allergy and Infectious Disease; Neuraxis; Neurocognitive; Neurologic; Outcome; Parents; Peripheral; Plasma; Prevention; Process; Protocols documentation; RNA; RNA Sequences; Reliance; SIV; Staging; T cell response; T-Cell Activation; Thailand; Tropism; Variant; Viral; Virus; animal data; central nervous system injury; cytokine; genome sequencing; immune activation; macrophage; monocyte; neuropsychological; prevent; transmission process

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.

描述(由申请人提供)：在急性艾滋病毒期间发生的全身免疫反应和中枢神经系统(CNS)事件可能为与艾滋病毒相关的慢性中枢神经系统损伤和与中枢神经系统相关的艾滋病毒宿主的建立奠定基础。正如最早的系统特征，如血浆HIV RNA峰值、T细胞激活水平和早期CD4细胞丧失是HIV疾病轨迹的关键决定因素，在早期阶段启动的CNS过程可能对CNS相关病毒库的建立、CNS区段病毒的建立、宿主控制CNS病毒的能力以及感染的长期CNS后果起关键作用。后勤方面的挑战导致严重依赖动物数据来定义急性艾滋病毒期间可能发生的中枢神经系统事件。在这项申请中，我们扩展了与美国陆军在泰国正在进行的研究的现有合作伙伴关系，以确定这些最早的人类事件，并确定影响CNS长期结果的因素。这项申请建议为60名泰国受试者提供集中的中枢神经系统特征，这些受试者在急性HIV感染期间(暴露后1个月)登记。在我们的方案中，一半的受试者将在为期18个月的固定课程的初步评估后立即开始HAART。我们将纵向表征CNS临床事件、神经、神经心理和精神因素、多模式磁共振成像、脑脊液免疫学和隔室特定的全基因组HIV测序，以确定发生在急性HIV中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。母体研究包括广泛的系统免疫学和病毒学特征，使我们能够确定最早的系统事件是否会影响CNS的长期结果。