Impact of Cannabinoid Use on HIV-related Brain Alterations in Young Adults

 描述（由申请人提供）：拟议研究的目的是开发一种多模式方法，以阐明艾滋病毒感染和大麻使用对青年大脑的综合影响。越来越多的新人类免疫缺陷病毒（艾滋病毒）感染发生在青少年和年轻成年人，或青年，艾滋病毒感染者（YLWH; 2010年为25-30%）。YLWH正在完成中枢神经系统的发展，并将与艾滋病毒感染和相关治疗生活很长一段时间。来自成年人的证据表明，尽管进行了抗逆转录病毒治疗，但HIV感染仍对CNS产生影响;然而，我们对HIV感染及其治疗对YLWH CNS的影响知之甚少。最近的研究结果表明，行为感染的YLWH有明显的认知障碍，尽管因果关系尚不清楚，可能是多因素的。目前HIV相关神经发病机制的理论集中在全身性和神经炎症的作用上，尽管现有的发现主要来自对具有复杂合并症和治疗史的成人的研究。更好地了解中枢神经系统的变化，在行为感染的YLWH，然后，将提供重要的见解，并可能有临床意义的中枢神经系统发病机制。重要的是，这一队列的特点是大麻使用率高，这可能会影响艾滋病毒感染的进展以及相关的认知和神经改变。大麻素与更大的免疫抑制和感染易感性增加有关;然而，它们也可能改变细胞因子和趋化因子表达，从而驱动抗炎反应。文献表明，随着抗炎作用的平行，对更快疾病进展的易感性可能增加。青少年使用大麻与神经成像和认知功能的变化有着独立的联系。艾滋病毒感染和大麻使用对中枢神经系统的影响之间复杂的相互作用的可能性需要进一步调查，以指导制定相关的青年治疗干预措施。拟议的研究旨在通过研究YLWH（年龄18-24岁）和对照参与者，探索大麻使用对HIV相关CNS效应的影响，该研究采用跨学科方法，包括多模式神经影像学测量，炎症和免疫功能的血浆生物标志物以及神经认知结果。该试点项目将启动行为获得性艾滋病毒感染的中枢神经系统的影响的基本特征在YLWH;探索共病大麻使用的影响;启动炎症作为观察到的效果的介质的关键评估;并探索有前途的组合神经影像学，血浆生物标志物和临床变量为未来的研究。由此产生的研究结果将为多地点，多学科的调查奠定基础，通过表征艾滋病毒和青少年共病大麻使用的神经和炎症特征，并提出功能上有意义的生物标志物，用于识别有CNS下降风险的个体，监测与ART相关的有效性和毒性，并探索与其他常见滥用物质的相互作用。

 DESCRIPTION (provided by applicant): The purpose of the proposed research is to develop a multimodal approach to elucidate the combined effects of HIV infection and cannabis use on the brain in youth. An increasing proportion of new human immunodeficiency virus (HIV) infections occur in adolescents and young adults, or youth, living with HIV (YLWH; 25-30% in 2010). YLWH are in the midst of completing CNS development and will live with HIV infection and associated treatment for a long time. Evidence from adults suggests continuing CNS effects of HIV infection despite antiretroviral therapy; however, we know little about the impact of HIV infection and its treatments on the CNS in YLWH. Recent findings suggest significant cognitive impairments in behaviorally- infected YLWH, although the causal factors are unknown and likely multifactorial. Current theories of HIV- associated neuropathogenesis focus on the role of systemic and neural inflammation, although existing findings come largely from studies of adults with complex comorbidities and treatment histories. A better understanding of CNS changes in behaviorally-infected YLWH, then, will provide important insight and may have clinical implications regarding CNS pathogenesis. Of importance, this cohort is characterized by a high rate of cannabis use, which may impact the progression of HIV infection and associated cognitive and neurological alterations. Cannabinoids have been linked to greater immune suppression and increased vulnerability to infection; however, they also may alter cytokine and chemokine expression, driving an anti- inflammatory response. The literature suggests a potential increase in susceptibility to more rapid disease progression alongside parallel anti-inflammatory effects. Cannabis use in adolescence has been linked independently to changes in neuroimaging and cognitive functioning. The possibility of complex interplay among the CNS effects of HIV infection and cannabis use requires further investigation for guidance on the development of relevant treatment interventions in youth. The proposed study aims to explore the impact of cannabis use on HIV-associated CNS effects by studying YLWH (age 18-24) and control participants using an interdisciplinary approach that will include multimodal neuroimaging measures, plasma biomarkers of inflammation and immune function, and neurocognitive outcomes. This pilot project will initiate an essential characterization of the CNS effects of behaviorally-acquired HIV infection in YLWH; explore the impact of comorbid cannabis use; initiate the critical assessment of inflammation as a mediator of observed effects; and explore promising combinations of neuroimaging, plasma biomarker, and clinical variables for future studies. The resultant findings will set the stage for multisite, multi-disciplinary investigations by characterizing the neurologic and inflammatory signatures of HIV and comorbid cannabis use in youth and suggesting functionally meaningful biomarkers for identifying individuals at risk for CNS decline, monitoring effectiveness and toxicity associated with ART, and exploring interactions with other common substances of abuse.