Central Nervous System Effects in Acute HIV Seroconversion

中枢神经系统对急性 HIV 血清转化的影响

• 批准号: 7880896
• 负责人: VICTOR VALCOUR
• 金额: $ 17.45万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880896
• 关键词: AIDS neuropathy; Acute; Affect; Area; Attenuated; Autopsy; Biological Assay; Blood; Brain; Brain Injuries; Brain region; CCL2 gene; Cerebrospinal Fluid; Choline; Clinical; Clinical Data; Collaborations; DNA; Data; Department of Defense; Disease; Enrollment; Environment; Enzyme Immunoassay; Epidemic; Evaluation; Event; Funding; Future; Generations; Goals; HIV; HIV Antibodies; HIV Infections; HIV Seropositivity; Hawaii; Highly Active Antiretroviral Therapy; Image; Immune; Individual; Infection; Infectious Diseases Research; Inflammation; Injury; Interleukin-6; International; Intervention; Laboratories; Letters; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Medical; Military Personnel; Mucous Membrane; N-acetylaspartate; Neopterin; Neuraxis; Neurologic; Neurologic Manifestations; Neuronal Injury; Neuropsychological Tests; Nucleic Acid Amplification Tests; Nucleic Acids; Peripheral; Peripheral Blood Mononuclear Cell; Phase; Plasma; Protocols documentation; Research; Research Institute; Resources; Retrovirology; Science; Site; Southeastern Asia; Spinal Puncture; Staging; Thailand; Time; Viral; Work; arm; base; cohort; cost; falls; immune activation; interest; myoinositol; neuropsychological; operation; programs; psychologic; public health relevance; tau Proteins; vaccine development

DESCRIPTION (provided by applicant): It is increasingly evident that the events which occur during acute HIV infection have a lasting impact on HIV disease course. Brain injury may occur in this very early stage, a factor that is sometime clinically evident with neurological manifestations of disease and is thought to have long-standing consequences. To date, our understanding of these earliest CNS effects are limited since capturing clinical data in the weeks following infection requires extensive resources and since such individuals seldom succumb to autopsy. Information relating to the first few weeks following infection is particularly lacking as few centers are able to identify infection in this very early phase. Intensive neurological and psychological characterization of acute infection would greatly advance our understanding of brain injury in HIV. Our collaborative organization in Bangkok, Thailand, known as the Southeast Asia Research Collaboration with Hawaii (SEARCH), will launch a US Department of Defense-funded protocol in the fall of 2008 to capture up to thirty acute HIV-infected cases in 2 years. All individuals will have been infected within the three weeks prior to enrollment (HIV antibody negative, nucleic acid positive). Broadly focused on vaccine development goals to characterize immunological changes associated with acute infection and the potential impact of mega- HAART in early infection, this cohort provides an unmatched opportunity to assess the neurological manifestations of HIV during acute HIV infection in a predominantly non-subtype B epidemic. In this application, we propose to acquire MR Spectroscopy, neurological assessments, neuropsychological testing, psychiatric characterization and cerebrospinal fluid (CSF) in twenty such cases at baseline and longitudinally for 96 weeks. Our primary goal is to quantify brain injury and CNS inflammation during this early phase of infection and to correlate these parameters to intracellular HIV DNA and systemic immune status during the acute HIV infection period. We will also store peripheral blood mononuclear cells (PBMC) and CSF for future collaborative studies with particular interest in viral sequencing in blood and CSF. PUBLIC HEALTH RELEVANCE: This project will aid in clarifying the earliest events during HIV infection with regard to brain injury to determine the extent to which the brain is affected immediately after infection.

描述（由申请人提供）：越来越明显的是，急性艾滋病毒感染期间发生的事件对艾滋病毒疾病病程具有持久的影响。脑损伤可能会在这个早期阶段发生，这是疾病神经系统表现在临床上有时显而易见的因素，并且被认为会产生长期的后果。迄今为止，我们对这些最早的CNS效应的理解是有限的，因为在感染后的几周内捕获临床数据需要广泛的资源，并且由于这些人很少屈服于尸检。与感染后的前几周有关的信息尤其缺乏，因为很少有中心能够在这一早期阶段识别感染。急性感染的密集神经系统和心理特征将大大提高我们对艾滋病毒中脑损伤的理解。我们在泰国曼谷的合作组织与夏威夷的东南亚研究合作（SEECH）将于2008年秋季启动美国国防部资助的协议，以在2年内捕获多达30个急性HIV感染的病例。所有个体都将在入学前三周内被感染（HIV抗体阴性，核酸阳性）。该队列广泛关注疫苗发育目标，以表征与急性感染相关的免疫变化以及巨型HAART在早期感染中的潜在影响，为评估急性HIV感染期间HIV的神经系统表现提供了一个无与伦比的机会，在主要非补充型疾病中的急性HIV感染中。在此应用中，我们建议在基线和纵向持续96周的二十例此类情况下，在二十个这样的情况下获得MR光谱，神经系统评估，神经心理学测试，精神病表征和脑脊液（CSF）。我们的主要目标是在感染的早期阶段量化脑损伤和中枢神经系统炎症，并将这些参数与急性HIV感染期间的细胞内HIV DNA和全身免疫状态相关联。我们还将存储外周血单核细胞（PBMC）和CSF，以进行未来的协作研究，并特别感兴趣血液和CSF的病毒测序。公共卫生相关性：该项目将有助于阐明脑损伤中艾滋病毒感染期间最早的事件，以确定感染后立即影响大脑的程度。