Examining a Biopsychosocial Model of Neurocognitive Health for HIV-positive Sexual Minority Men

项目总结/摘要 神经认知障碍（NCI）对艾滋病毒阳性人群的影响不成比例，因为艾滋病毒感染者的高度 艾滋病危机。虽然现代抗逆转录病毒疗法大大延长了寿命，但总体而言， 艾滋病毒相关的神经认知障碍（HAND）的患病率三十年来一直保持稳定。性 少数民族男性（SMM）占美国所有艾滋病毒诊断的大多数。 疫情然而，很少有研究探讨了SMM可能相应地被过度代表的概念 受NCI影响的HIV+个体比例很高。此外，对HAND病因学的理解是 目前有限，这阻碍了经验支持的预防和治疗的发展 手的策略。研究表明，艾滋病毒感染的慢性炎症作用使艾滋病毒+ NCI的风险较高，但尽管对神经炎症有共同的脆弱性，但大约一半的人 的HIV+个体在整个生命周期中表现出规范的认知功能，这表明个体水平 背景因素是认知风险和复原力的基础。慢性压力也与 神经炎症，通过增加促炎细胞因子。建立在症状和 少数民族的压力，这项调查是基于一个新的假设，社会结构的综合因素（例如， 贫困、创伤）与少数民族压力（即，慢性心理压力 性身份）以减少认知储备（即，神经元对损伤的恢复力）。而且我们 假设慢性高水平炎性细胞因子代表了潜在的致病机制 少数族裔压力对认知健康产生负面影响。因此，该项目侧重于三个目标： (1)为了检验该假设NCI风险将随着心理（即，少数民族压力）和 社会结构性综合征（例如，低教育，无家可归）因素报告的艾滋病毒+SMM;（2）检查 少数民族压力和社会结构性流行病脆弱性对NCI风险交互影响;（3）评估 升高的促炎细胞因子的介导作用（例如，IL-6）在假设的 少数民族压力和NCI风险。拟定项目将纳入一项更大的研究（R01MH114735，PI： Rendina），在此称为母项目，该项目正在积极招募250名HIV + SMM，以检查 少数民族和艾滋病毒相关的压力对心理，行为和免疫健康结果的作用。的 拟议的项目将在母项目现有的神经认知测试组合中增加一项评估， 更细致入微地了解HIV + SMM的认知健康状况。研究和培训 我精心设计了指导这一建议的计划，以优化我正在进行的博士培训经验 培养我成为未来的独立研究科学家

PROJECT SUMMARY/ABSTRACT Neurocognitive impairment (NCI) has disproportionately impacted the HIV+ population since the height of the AIDS crisis. Though modern antiretroviral therapy has afforded vast improvements in longevity, the overall prevalence of HIV-associated neurocognitive disorders (HAND) has remained stable for three decades. Sexual minority men (SMM) have comprised the majority of all HIV diagnoses in the U.S. for the duration of the epidemic. However, few studies have explored the notion that SMM may be correspondingly overrepresented in the high proportion of HIV+ individuals impacted by NCI. Moreover, understanding of HAND etiology is currently limited, which has hindered the development of empirically supported prevention and treatment strategies for HAND. Research suggests that the chronic inflammatory action of HIV infection places HIV+ individuals at a higher risk for NCI, but despite common vulnerability to neuroinflammation, approximately half of HIV+ individuals exhibit normative cognitive function across the lifespan, suggesting that individual-level contextual factors underlie cognitive risk and resiliency. Chronic stress has also been associated with neuroinflammation, via increases in pro-inflammatory cytokines. Building upon theories of syndemics and minority stress, this investigation is based on a novel hypothesis that socio-structural syndemic factors (e.g., poverty, trauma) additively interact with minority stress (i.e., chronic psychological stress related to one’s sexual identity) to diminish cognitive reserve (i.e., neuronal resilience against injury). Furthermore, we hypothesize that chronically high levels of inflammatory cytokines represent a potential causative mechanism through which minority stress negatively impacts cognitive health. As such, the project focuses on three aims: (1) to test the hypothesis the NCI risk will increase with the number of psychological (i.e., minority stress) and socio-structural syndemic (e.g., low education, homelessness) factors reported by HIV+SMM; (2) examine the interactive impact of minority stress and socio-structural syndemic vulnerabilities on NCI risk; and (3) assess the mediating role of elevated pro-inflammatory cytokines (e.g., IL-6) in the hypothesized association between minority stress and NCI risk. The proposed project will be embedded into a larger study (R01MH114735, PI: Rendina), referred to herein as the parent project, which is actively enrolling 250 HIV+ SMM to examine the role of minority and HIV-related stress on psychological, behavioral, and immunological health outcomes. The proposed project will add one assessment to the parent project’s existing neurocognitive test battery to allow for a more nuanced understanding of the cognitive health profile of HIV+ SMM. The research and training plans guiding this proposal have been carefully crafted to optimize my ongoing doctoral training experiences and foster my development as a future independent research scientist.