Evaluation of Neurobiological Mechanisms Mediating the Effect of Immune Activation on Neurocognitive Impairment and the Role of Psychosocial Factors Among Women Living with HIV
免疫激活对神经认知障碍影响的神经生物学机制的评估以及女性艾滋病毒感染者心理社会因素的作用
基本信息
- 批准号:10534423
- 负责人:
- 金额:$ 71.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-13 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdherenceAffectAgeAgingAttentionBehavior TherapyBehavioralBiologicalBiological MarkersChronicChronic stressClinicalCognitiveDataDevelopmentDiscriminationDopamineDopamine Uptake InhibitorsEtiologyEvaluationGoalsHIVHIV SeronegativityHairImmuneImmunologic MarkersImmunotherapyImpaired cognitionIndividualInflammatoryInfrastructureInterleukin-6InterventionKnowledgeLeadLearningLettersLifeLightLinkLongitudinal StudiesMediatingMental DepressionMental HealthMetabolismNeurobiologyNeurocognitive DeficitNeuronsNeuropsychologyNeurotransmittersNorepinephrineOutcomePathway interactionsPersonsPhenotypePhenylalaninePhenylalanine Metabolism PathwayPreventionPsychosocial FactorQuinolinic AcidRiskRisk FactorsRoleSerotoninShort-Term MemorySocial supportSpecimenTNF geneTimeTreatment/Psychosocial EffectsTryptophan Metabolism PathwayViralWomanWomen&aposs GroupWomen&aposs Interagency HIV StudyWorkagedantiretroviral therapybehavioral pharmacologybiopsychosocialcognitive functioncost effectiveexecutive functionexperiencehigh riskimmune activationimprovedmenmulti-component interventionnegative affectnerve injuryneurobiological mechanismneurofilamentneurotoxicpsychosocialpublic health prioritiesracial diversityresiliencesexsocial stigmasubstance usetherapy adherence
项目摘要
PROJECT ABSTRACT/SUMMARY. The proposed R01 is built upon the premise that: 1) Cognitive impairment
(CI) persists even in the context of HIV viral suppression; 2) women living with HIV (WLWH) experience
disproportionate burden of CI and have higher rates of, and stronger associations with, many of the underlying
biopsychosocial risk factors for CI, as well as unique sex-specific risk factors; 3) immune activation persists in
the context of viral suppression; 4) immune activation (e.g., Interleukin[IL]-6, sCD163) is a consistent risk factor
of CI in HIV; 5) neurobiological pathways affecting cognitive functions are activated by HIV directly and indirectly
through immune activation; 6) psychosocial factors such as stigma/discrimination, depression, and substance
use impair cognitive functions and are associated with heightened immune activation, likely both directly and
indirectly through reduced ART levels. By leveraging the strong infrastructure of the Women's Interagency
HIV Study (WIHS), including existing behavioral data and specimen, the current longitudinal study will
fill significant gaps in the field by examining the role of the neurobiological pathways whereby chronic
immune activation leads to CI phenotypes in a large phenotypically well-defined group of WLWH. In a
highly cost-effective approach, we will use existing biospecimen to assess biomarkers of chronic immune
activation and neurobiological pathways and link them to existing neuropsychological assessments among
N=500 WLWH aged 26 and older (Median age = 50) at 3 time points, to assess the following aims: Aim 1. To
examine neurobiological pathways mediating the link between chronic immune activation and CI phenotypes in
WLWH. Aim 2. To identify psychosocial factors affecting immune activation and neurobiological pathways. Aim
3. To examine the role of ART hair levels in mediating the effect of psychosocial factors in Aim 2 on immune
activation and neurobiological pathway biomarkers. Impact. The results of this study will have several important
clinical implications for the prevention and treatment of CI in WLWH, including behavioral and pharmacological
therapies. Understanding the unique impact of biomarkers on cognitive outcomes will provide guidance on
clinical intervention targets (e.g., immune therapy, dopamine reuptake inhibitors). Understanding the role of
psychosocial factors in modulating immune activation and neurobiological pathways and the mediating role of
ART adherence level, will inform behavioral intervention strategies (e.g., resilience, social support). Psychosocial
factors may be particularly ideal intervention targets to curb the inflammatory cascade leading to CI.
项目摘要/总结。拟议的R 01是建立在以下前提下的:1)认知障碍
(CI)即使在抑制艾滋病毒的情况下也会持续存在; 2)女性艾滋病毒感染者(WLWH)的经历
不成比例的CI负担,并且与许多潜在的
CI的生物心理社会风险因素,以及独特的性别特异性风险因素; 3)免疫激活持续存在,
病毒抑制的背景; 4)免疫激活(例如,白细胞介素[IL]-6,sCD 163)是一个一致的风险因素
5)影响认知功能的神经生物学通路被HIV直接和间接激活
通过免疫激活; 6)心理社会因素,如耻辱/歧视,抑郁和物质
使用会损害认知功能,并与增强的免疫激活有关,可能直接和
通过降低抗逆转录病毒治疗水平间接地。通过利用妇女机构间组织的强大基础设施,
艾滋病毒研究(WIHS),包括现有的行为数据和标本,目前的纵向研究将
通过检查神经生物学通路的作用,填补了该领域的重大空白,
免疫激活导致在一个大的表型明确定义的WLWH组中的CI表型。中
高成本效益的方法,我们将使用现有的生物标本,以评估生物标志物的慢性免疫
激活和神经生物学途径,并将它们与现有的神经心理学评估联系起来,
在3个时间点,N=500名26岁及以上的WLWH(中位年龄= 50),以评估以下目标:目标1。到
研究介导慢性免疫激活和CI表型之间联系的神经生物学途径,
WLWH。目标2.确定影响免疫激活和神经生物学通路的心理社会因素。目的
3.研究ART毛发水平在介导Aim 2中的心理社会因素对免疫功能的影响中的作用,
激活和神经生物学途径生物标志物。冲击这项研究的结果将有几个重要的
在WLWH中预防和治疗CI的临床意义,包括行为和药理学
治疗了解生物标志物对认知结果的独特影响将为以下方面提供指导:
临床干预目标(例如,免疫疗法、多巴胺再摄取抑制剂)。理解的作用
调节免疫激活和神经生物学通路的心理社会因素以及
ART依从性水平,将告知行为干预策略(例如,社会支持(Social support)。心理社会
这些因子可能是抑制导致CI的炎症级联反应的特别理想的干预靶点。
项目成果
期刊论文数量(0)
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Andrea Norcini Pala其他文献
Andrea Norcini Pala的其他文献
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{{ truncateString('Andrea Norcini Pala', 18)}}的其他基金
Evaluation of Neurobiological Mechanisms Mediating the Effect of Immune Activation on Neurocognitive Impairment and the Role of Psychosocial Factors Among Women Living with HIV
免疫激活对神经认知障碍影响的神经生物学机制的评估以及女性艾滋病毒感染者心理社会因素的作用
- 批准号:
10704105 - 财政年份:2022
- 资助金额:
$ 71.2万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10679092 - 财政年份:2021
- 资助金额:
$ 71.2万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10432133 - 财政年份:2021
- 资助金额:
$ 71.2万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10327065 - 财政年份:2021
- 资助金额:
$ 71.2万 - 项目类别:
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