Correlates of Monocyte-Associated Virus in HIV Neurocognitive Impairment

单核细胞相关病毒与 HIV 神经认知损伤的相关性

• 批准号: 8252202
• 负责人: WILLIAM Albert BLATTNER
• 金额: $ 64.55万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8252202
• 关键词: AIDS Dementia Complex; Acquired Immunodeficiency Syndrome; Address; Adverse effects; Affect; African; Anti-Retroviral Agents; Applications Grants; Attention; Binding Sites; Blood; Blood - brain barrier anatomy; Blood Cells; Brain; CD14 gene; California; Cells; Cerebrospinal Fluid; Classification; Clinical; Comorbidity; Coupled; Cross-Sectional Studies; DNA; Data; Development; Drug resistance; Enrollment; Frequencies; Future; Genotype; HIV; HIV Infections; HIV encephalitis; HIV-1; Human Virology; Impairment; Individual; Inflammatory; Institutes; Laboratories; Link; Manuscripts; Maryland; Measurement; Measures; Molecular Virology; Mononuclear; Mus; Natural History; Neurocognitive; Neuropsychological Tests; Nigeria; Outcome; Pathogenesis; Patients; Pattern; Penetrance; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Plasma; Plasma Cells; Preparation; Process; Proviruses; Public Health; RNA; Recruitment Activity; Regulator Genes; Reporting; Research; Research Personnel; Role; Sahara; Satellite Viruses; Scientist; Severities; Techniques; Testing; Tropism; Universities; Viral; Viral Drug Resistance; Viral Load result; Virus; brain tissue; cohort; env Genes; follow-up; improved; international center; macrophage; mild neurocognitive impairment; monocyte; neurobehavioral; pol genes; programs; prospective; public health relevance; repository; residence; response; success; trafficking; treatment adherence; treatment response; viral RNA

DESCRIPTION (provided by applicant): Improved and more sensitive techniques for detecting the range of HIV-induced neurocognitive impairment (NCI) [asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) or HIV-associated dementia (HAD)] document NCI as a major co-morbidity of HIV-1 (HIV) infection. Building on the confluence of new information showing that CD14-positive Monocyte-associated HIV DNA Viral Load (CD14MADVL) correlates with NCI, coupled to unpublished data from co-investigator S. Gartner documenting a highly distinct virus in CD14 positive monocyte, the current proposal targets in depth pathogenesis research of the virus in this compartment drawing from a unique prospective cohort of treatment naive patients recruited from a large Nigerian PEPFAR program. The conceptual framework for this project draws from the well established fact that HIV enters the brain primarily via the trafficking of infected blood monocytes and virus in this compartment provides a window for understanding the pathogenesis of NCI without direct access to brain tissue. Our preliminary studies document capacity to enroll and detect large numbers of treatment naive patients with NCI, maintain them in prospective follow up and perform in depth laboratory analysis of the virus from monocytes, CD-14 negative mononuclear cells, plasma and CSF. The central hypothesis of this grant application is that the previously reported correlation between severity of NCI and CD14MADVL is linked to a distinctive pattern of viral quasi-species in this compartment (unpublished preliminary data) and that detailed analysis of viral motifs among the quasi-species from this compartment compared to non-monocyte HIV DNA and plasma viral RNA offer promise for identifying signature patterns that will inform NCI pathogenesis. This hypothesis will be addressed in two aims: Aim 1 - Classification of NCI and correlation with CD14MADVL in cross sectional study and longitudinally, and Aim 2 - Detailed study of the virus engaging targeted quasi-species analysis to characterize distinguishing motifs associated with NCI, and to study the relationship to viral subtype and the relationship of viral drug resistance in different compartments to NCI. The research team is comprised of internationally recognized HIV, neuro-AIDS and molecular virology experts from the University of Maryland, leading neuro-AIDS scientists from the University of California San Diego HIV Neurobehavioral Research Center (UCSD/HNRC), and local research investigators from the Institute of Human Virology-Nigeria (IHV-N) and affiliates in Nigeria. Additionally an extensive repository of viable peripheral blood cells, DNA and plasma will be collected for future studies. PUBLIC HEALTH RELEVANCE: The public health implications are that a high frequency of impairment in the ability of people to think clearly due to HIV infection can have adverse effects on treatment success. The current project will provide information on how frequently this impairment occurs and to understand how the virus causes this impairment.

描述（由申请人提供）：用于检测HIV诱导的神经认知障碍（NCI）[无症状神经认知障碍（ANI），轻度神经认知障碍（MND）或HIV相关痴呆症（HAT）]文档NCI的技术改进和更敏感的技术，如HIV，HIV（HIV）是主要的，HIV（HIV）（HARI）相关（HAT）。建立在新信息的汇合基础上，表明CD14阳性与单核细胞相关的HIV DNA病毒载量（CD14MADVL）与NCI相关，并与共同投资者S. Gartner相关的数据与未公开的数据相关，记录了CD14正面单核的prosposition中的一项独特的prothertists，该研究构成了这种构成的病毒性，该研究构成了这种构成的病毒性，该研究的构成了该病毒pterive，该研究的构成了这种构成的病毒性，该病毒构成了该病毒的病毒性。从尼日利亚大型PEPFAR计划中招募的幼稚患者。该项目的概念框架源于以下事实，即艾滋病毒主要通过在该室内贩运感染的血单核细胞和病毒进入大脑，这为理解NCI的发病机理提供了一个窗口，而无需直接进入脑组织。我们的初步研究记录了注册和检测大量NCI治疗患者的能力，将其保持前瞻性随访，并深入实验室分析单核细胞，CD-14阴性单核细胞，血浆和CSF。该赠款应用的核心假设是，NCI和CD14MADVL的严重程度之间的相关性与此隔间中病毒性准物种的独特模式有关（未发表的初步数据），并详细介绍了该阶段中的ncor式识别模式的详细分析，以识别该阶段的模式，以识别型号的识别型号，以识别型号。将告知NCI发病机理。该假设将在两个目的中解决：目标1-在横截面研究和纵向研究中与CD14MADVL的分类和与CD14MADVL的相关性，并在纵向上进行纵向研究，并详细研究具有与NCI相关的与NCI相关的靶向靶向准物种分析，以表征与Viral subtype contanc and conters conters and conters ncters nict and nc conterance and conters nict and conters ncter and conters nc converance and ncters conters conters and nc conters n.研究小组由马里兰州大学的国际认可的HIV，神经辅助和分子病毒学专家组成，来自加利福尼亚大学圣地亚哥大学HIV HIV神经黑人研究中心（UCSD/HNRC）的领先的神经辅助科学家以及人类病毒学研究所的本地研究研究者（NRC）。另外，将收集一个可行的外围血细胞，DNA和血浆的广泛存储库，以进行以后的研究。 公共卫生的相关性：公共卫生的影响是，由于艾滋病毒感染，人们清楚地思考能力的高频损害可能会对治疗成功产生不利影响。当前的项目将提供有关这种损害发生多久的信息，并了解病毒如何导致这种损害。