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

基本信息

项目摘要

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showing that CD14-positive Monocyte-associated HIV DNA Viral Load (CD14MADVL) correlates with NCI, coupled to unpublished data from co-investigator S. Gartner documenting a highly distinct virus in CD14 positive monocyte, the current proposal targets in depth pathogenesis research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between severity of NCI and CD14MADVL is linked to a distinctive pattern of viral quasi-species in this compartment (unpublished preliminary data) and that detailed analysis of viral motifs among the quasi-species from this compartment compared to non-monocyte HIV DNA and plasma viral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):改进和更敏感的检测HIV诱导的神经认知障碍(NCI)范围的技术[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(HAD)]证明NCI是HIV-1 (HIV)感染的主要合并症。基于显示CD14阳性单核细胞相关HIV DNA病毒载量(CD14MADVL)与NCI相关的新信息的融合,再加上合作研究者S. Gartner未发表的数据,记录了CD14阳性单核细胞中高度不同的病毒,目前的建议目标是在该隔间中对病毒进行深入的发病机制研究,这些研究来自尼日利亚PEPFAR项目中招募的一组独特的前瞻性治疗初治患者。这个项目的概念框架来自一个公认的事实,即艾滋病毒主要通过被感染的血液单核细胞的贩运进入大脑,而病毒在这个隔室中为理解NCI的发病机制提供了一个窗口,而不直接进入脑组织。我们的初步研究证明有能力招募和检测大量未接受治疗的NCI患者,对他们进行前瞻性随访,并对来自单核细胞、CD-14阴性单核细胞、血浆和脑脊液的病毒进行深入的实验室分析。该资助申请的中心假设是,先前报道的NCI严重程度与CD14MADVL之间的相关性与该隔室中病毒准物种的独特模式有关(未发表的初步数据),并且与非单核细胞HIV DNA和血浆病毒RNA相比,该隔室中准物种中的病毒基序的详细分析为识别将通知NCI发病机制的特征模式提供了希望。这一假设将在两个目标中得到解决:目标1 - NCI的分类以及与CD14MADVL在横断面和纵向研究中的相关性;目标2 -利用靶向准种分析对病毒进行详细研究,以表征与NCI相关的区分基序,并研究与病毒亚型的关系以及不同区室中病毒对NCI的耐药性关系。该研究小组由来自马里兰大学的国际公认的艾滋病毒、神经艾滋病和分子病毒学专家、来自加州大学圣地亚哥分校艾滋病毒神经行为研究中心(UCSD/HNRC)的主要神经艾滋病科学家以及来自尼日利亚人类病毒学研究所(IHV-N)及其分支机构的当地研究人员组成。此外,还将收集大量的活外周血细胞、DNA和血浆,以供将来的研究使用。

项目成果

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WILLIAM Albert BLATTNER其他文献

WILLIAM Albert BLATTNER的其他文献

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{{ truncateString('WILLIAM Albert BLATTNER', 18)}}的其他基金

NIGERIAN ALLIANCE FOR HEALTH SYSTEMS STRENGHENING (NAHSS)
尼日利亚加强卫生系统联盟 (NAHSS)
  • 批准号:
    8452446
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
NIGERIAN ALLIANCE FOR HEALTH SYSTEMS STRENGHENING (NAHSS)
尼日利亚加强卫生系统联盟 (NAHSS)
  • 批准号:
    8540158
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
NIGERIAN ALLIANCE FOR HEALTH SYSTEMS STRENGHENING (NAHSS)
尼日利亚加强卫生系统联盟 (NAHSS)
  • 批准号:
    8754493
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
NIGERIAN ALLIANCE FOR HEALTH SYSTEMS STRENGHENING (NAHSS)
尼日利亚加强卫生系统联盟 (NAHSS)
  • 批准号:
    8707788
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
GH12-1230, NIGERIA, NIGERIAN ALLIANCE FOR HEALTH SYSTEMS STRENGTHENING (NAHSS)
GH12-1230,尼日利亚,尼日利亚卫生系统加强联盟 (NAHSS)
  • 批准号:
    9025975
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
TRUST
相信
  • 批准号:
    8298868
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
TRUST
相信
  • 批准号:
    8547106
  • 财政年份:
    2012
  • 资助金额:
    $ 66.16万
  • 项目类别:
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:
    8625334
  • 财政年份:
    2010
  • 资助金额:
    $ 66.16万
  • 项目类别:
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
  • 财政年份:
    2010
  • 资助金额:
    $ 66.16万
  • 项目类别:
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:
    8427365
  • 财政年份:
    2010
  • 资助金额:
    $ 66.16万
  • 项目类别:

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