Integration and Analysis of Diverse HIV-Associated Data in CHARTER

CHARTER 中各种 HIV 相关数据的整合和分析

• 批准号: 8723636
• 负责人: KUMUD K SINGH
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-09 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723636
• 关键词: Acquired Immunodeficiency Syndrome; Age; Anti-Retroviral Agents; Antigen-Antibody Complex; Applications Grants; Atrophic; Binding; Brain; Brain Injuries; Brain imaging; CD4 Lymphocyte Count; Choline; Chronic; Clinical; Clinical Data; Cohort Studies; Collaborations; Complement; Complement 1q; Complement Activation; Complex; Consequences of HIV; Data; Data Collection; Data Set; Descriptor; Development; Disease; Enrollment; Ethnic Origin; Etiology; Genes; Genetic; Genotype; HIV; HIV Envelope Protein gp120; HIV Infections; HIV envelope protein; HIV-1; Highly Active Antiretroviral Therapy; Immune response; Immunologics; Impairment; Individual; Infection; Inflammatory Response; Inositol; Laboratories; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mannose; Mannose Binding Lectin; Mannose-Binding Lectins; Mediating; Modeling; N-acetylaspartate; Nerve Degeneration; Nervous System Physiology; Neuraxis; Neurocognitive; Neurocognitive Deficit; Outcome; Pathway interactions; Pharmaceutical Preparations; Pilot Projects; Prevention; Proteins; Race; Recording of previous events; Records; Research; Risk; Sex Education; Testing; Therapeutic Intervention; Time; Viral Load result; base; cohort; complement pathway; cytokine; demographics; follow-up; genome wide association study; gray matter; multidisciplinary; neurobehavioral; neuroimaging; neuroinflammation; neuropathology; neuropsychological; novel; novel marker; peripheral blood; predictive modeling; psychosocial; public health relevance; response; synaptogenesis; white matter

DESCRIPTION (provided by applicant): Chronic infection of HIV and its treatment with antiretrovirals have impacted the neurobehavioral and psychosocial functioning and resulted in complicated profiles of central nervous system. In order to understand and analyze these, advanced statistical approaches and larger integrated datasets are required for analyzing interactions among the multidimensional and multidisciplinary data. Furthermore, these approaches need to apply both the baseline and longitudinal data sets to predict the risk and progression of neuropathology, neurobehavioral and neuropsychological consequences for the identification and development of novel preventative and therapeutic interventions. In this R03 application we propose to do secondary analyses of already collected diverse HIV-associated data from well-studied and well-characterized CHARTER (CNS HIV Anti-Retroviral Therapy Effects Research) cohort by integrating and organizing these data for elucidating their complex interactions (aim 1) and develop predictive quantitative model (aim 2) that can identify subjects who are at greater risk for adverse neurobehavioral and/or psychosocial outcomes as a consequence of HIV and its treatments. We propose to focus on complement activation pathway - a specific innate immune response mechanism that is implicated in several neurodegenerative and neuroinflammatory diseases and it also mounts a critical anti-HIV response in peripheral blood and CNS. All three complement activation pathways, namely classical pathway through C1q, alternate pathway through HIV envelope proteins; and mannose binding lectin- mediated pathway activated by the MBL binding to the mannose residues on HIV gp120 or gp41 proteins; potentially interact with HIV. The aim of this proposal is to maximize the full value of previously collected data from CHARTER cohort as well as ongoing data collection to enhance our understanding of etiology and trajectories of HIV-associated neurobehavioral and neuropsychosocial consequences and to help identify novel markers for effective prevention and treatment. We propose to integrate and analyze diverse complement activation pathway genetics, inflammatory response, virologic and immunologic and neuropsychological data and brain imaging records to develop quantitative predictive models to identify subjects at greater risk for adverse neurocognitive outcomes as a consequence of HIV infection and antiretroviral treatment at the time of enrollment and in the longitudinal CHARTER cohort. The secondary analysis and pilot predictive modeling developed form these studies will be further tested for larger number of genes and in collaboration with larger cohorts such as Multicenter AIDS Cohort Study (MACS). Integration and analyses of multi-disciplinary data will better inform the predictability and management of HIV-associated neurocognitive disorders.

描述（由申请人提供）：HIV的慢性感染及其用抗逆转录病毒的治疗影响了神经行为和社会心理功能，并导致了中枢神经系统的复杂特征。为了理解和分析这些，需要进行高级统计方法和更大的集成数据集，以分析多维和多学科数据之间的相互作用。此外，这些方法需要应用基线和纵向数据集来预测神经病理学，神经行为和神经心理学后果的风险和进展，以鉴定和发展新型预防和治疗干预措施。在此R03应用中，我们建议对已经收集的HIV相关数据进行二次分析，并通过良好的和良好的特征宪章（CNS HIV HIV抗病毒疗法效应研究）共同整合和组织这些数据，通过整合和组织这些数据来阐明其复杂的相互作用（AIM 1），并在更大的量子上识别量子的量子（目标1），以识别有效的量子量，以供应量的量子量表2和/或由于艾滋病毒及其治疗而产生的社会心理结局。我们建议专注于补体激活途径 - 一种特定的先天免疫反应机制，与几种神经退行性和神经炎症性疾病有关，并且在外周血和CNS中也安装了关键的抗HIV反应。这三个补体激活途径，即穿过C1Q的经典途径，通过HIV包膜蛋白的交替途径； MBL与HIV GP120或GP41蛋白上的甘露糖残基激活的甘露糖结合介导的途径；潜在与HIV相互作用。该提案的目的是最大程度地提高宪章队列中先前收集的数据的全部价值，以及正在进行的数据收集，以增强我们对病因和HIV相关神经行为和神经心理社会的后果的理解，并帮助识别有效预防和治疗的新颖标记。我们建议整合和分析多样化的补体激活途径遗传学，炎症反应，病毒学和免疫学和神经心理学数据和大脑成像记录，以开发定量预测模型，以识别受HIV感染的不良神经认知兴趣风险的受试者，这是HIV感染和抗雷术治疗的结果，并在富度术中进行了热情训练和持续型的行为。这些研究将进一步测试大量基因，并与较大的队列（例如多中心艾滋病队列研究（MAC））合作，将进一步测试次要分析和试点预测模型。多学科数据的整合和分析将更好地为与HIV相关的神经认知障碍的可预测性和管理提供信息。