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

基本信息

批准号：
8472533
负责人：
SERENA S SPUDICH
金额：
$ 59.08万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/8472533
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 Grant HIV HIV Genome 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

项目摘要

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）：急性HIV期间发生的全身免疫反应和中枢神经系统（CNS）事件可能为与慢性HIV相关的CNS损伤和CNS与CNS相关的HIV储量的建立奠定了基础。 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感染的后果。后勤挑战导致对动物数据的严重依赖，以定义急性HIV期间可能的中枢神经系统事件。在此应用程序中，我们扩展了与泰国美国陆军研究的现有合作伙伴关系，以定义人类中最早的事件，并确定影响长期CNS结果的因素。该申请建议为急性HIV期间入学的60名受试者（暴露后<1个月）提供密集的中枢神经系统表征。在我们的模式中，在初步评估固定的18个月课程后，将立即开始HAART的一半。我们将纵向表征CNS临床事件，神经系统，神经心理学和精神病因素，多模式磁共振成像，CSF免疫学和特定特异性的全基因组HIV测序，以确定急性HIV中发生的事件如何影响急性HIV影响慢性HIV CNS疾病。我们还将确定CNS创始人和建立病毒，并确定早期Haart干预是否影响这些关系。家长研究包括广泛的系统性免疫和病毒学特征，使我们能够确定最早的全身事件是否影响长期CNS结果。