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

 描述(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少年大脑的综合影响。越来越多的新的人类免疫缺陷病毒(HIV)感染发生在青少年和青壮年或青年艾滋病毒携带者(青年会；2010年为25%-30%)。青年会正在完成中枢神经系统的开发，并将长期与艾滋病毒感染和相关治疗生活在一起。来自成人的证据表明，尽管接受了抗逆转录病毒治疗，但艾滋病毒感染对中枢神经系统的影响仍在继续；然而，我们对艾滋病毒感染及其治疗对青瓦台医院中枢神经系统的影响知之甚少。最近的发现表明，行为感染的青少年儿童存在显著的认知障碍，尽管原因尚不清楚，可能是多因素造成的。目前关于HIV相关神经发病的理论主要集中在全身和神经炎症的作用上，尽管现有的发现主要来自对患有复杂共病和治疗史的成年人的研究。因此，更好地了解行为感染的YLWH中中枢神经系统的变化将提供重要的洞察力，并可能对CNS的发病机制具有临床意义。重要的是，这一群体的特点是大麻使用率很高，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。大麻素被认为与更强的免疫抑制和更容易受到感染有关；然而，它们也可能改变细胞因子和趋化因子的表达，推动抗炎反应。这些文献表明，伴随着抗炎作用，可能会增加对更快速的疾病进展的易感性。青春期大麻的使用与神经成像和认知功能的变化独立相关。艾滋病毒感染和大麻使用对中枢神经系统的影响之间可能存在复杂的相互作用，这需要进一步调查，以指导制定有关的青少年治疗干预措施。这项拟议的研究旨在通过研究YLWH(18-24岁)并使用包括多模式神经成像测量、血浆炎症和免疫功能生物标志物以及神经认知结果在内的跨学科方法来研究大麻使用对艾滋病毒相关中枢神经系统效应的影响。这一试点项目将启动对青瓦台医院行为获得性艾滋病毒感染的中枢神经系统影响的基本表征；探索并存使用大麻的影响；启动作为观察到的影响的中介的炎症的关键评估；并探索神经成像、血浆生物标记物和临床变量的有希望的组合，用于未来的研究。由此产生的发现将为多地点、多学科的调查奠定基础，通过表征青少年使用艾滋病毒和共病大麻的神经学和炎症特征，提出具有功能意义的生物标记物，用于识别中枢神经系统衰退的风险个体，监测与抗逆转录病毒治疗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.