Implications of cannabis use and cumulative adversity exposure for brain structure and function in young adults living with HIV.

抗逆转录病毒疗法(ART)减轻了但不是消除了 人类免疫缺陷病毒(HIV)。对认知和大脑完整性的影响现在更微妙，但长期 未知的长期影响，合并症中度、隐蔽或改善艾滋病毒的可能性 影响正变得越来越重要。年轻人(“青年”)新的艾滋病毒感染率和 未被充分研究的可能显著影响艾滋病毒中枢神经系统表现的常见合并症：大麻 利用和累积逆境。两者都可能改变免疫功能和炎症，作为其致病途径 除了它们的独立影响外，还对艾滋病毒的中枢神经系统效应产生影响。我们的初步数据显示，更糟糕的是 青年HIV感染者(YWH)的认知和神经成像结果与对照组(例如，记忆力较差和 执行功能，前额叶皮质变薄，使用脑磁图改变功能激活 [Meg])会减弱，或在某些情况下，因轻至中度但不是大量使用大麻而逆转。我们 假设与对照组相比，接受YWH治疗的患者的认知和神经成像结果更差 不使用大麻的情况将通过轻度到中度使用大麻而得到改善，而大量使用大麻 在两组中，频率将与更差的结果相关。重要的是，充分理解 艾滋病毒和大麻的相互作用可能需要考虑一生的逆境经历。强有力的证据 表明暴露在恶劣环境中，如虐待、暴力和压力，可以改变免疫力。 和中枢神经系统，这种接触在基督教青年会和类似的血清阴性风险群体中很常见。我们 将评估累积逆境在大麻和艾滋病毒的中介作用中的影响。建议进行的研究 将决定艾滋病毒、大麻和累积逆境对中枢神经系统结构和功能的交互影响 75名青少年儿童(年龄18-24岁)和75名可比对照组。我们将使用创新的神经成像方法(MEG到 测量功能活动和高级扩散方法)，以及大脑结构和新陈代谢 和神经认知评估。我们将审查艾滋病毒、大麻和累积逆境的调解 炎症和免疫激活的相互作用，使用血浆生物标记物进行评估。检查 这些影响对中枢神经系统功能和结构的相互作用将通过仔细的表征来促进 物质使用，评估累积的逆境负担，而不是单一的创伤事件，以及高级 统计技术。因此，我们将研究艾滋病毒和大麻对关键大脑系统的交互影响；模型 潜在机制；并考察一个重要但尚未得到充分研究的影响--累积逆境。这个 这项研究可能会产生很大的影响，因为它可以改善对艾滋病毒中枢神经系统影响的检测，以及我们对 发病机制。它将能够更好地预防中枢神经系统衰退，制定针对中枢神经系统的治疗方案，并 治疗策略，以及总体上减轻艾滋病毒对早期感染个人的中枢神经系统的影响 而且仍处于神经发育阶段，早期发现可能会有最大的好处。

Antiretroviral therapy (ART) has lessened but not eliminated the central nervous system (CNS) impact of human immunodeficiency virus (HIV). With effects on cognition and brain integrity now subtler, yet chronic with unknown long-term implications, the potential of comorbid conditions to moderate, obscure or ameliorate HIV effects is increasingly important. Young adults (“youth”) have high rates of both new HIV infection and understudied common comorbidities with significant potential to influence HIV’s CNS presentation: cannabis use and cumulative adversity. Both may alter immune functioning and inflammation as pathways for their influence on HIV’s CNS effects, in addition to their independent impact. Our preliminary data show that worse cognitive and neuroimaging outcomes in youth with HIV (YWH) compared to controls (e.g., worse memory and executive functioning, thinner prefrontal cortex, altered functional activation using magnetoencephalography [MEG]) are attenuated or, in some cases, reversed by light to moderate, but not heavy, cannabis use. We hypothesize that worse cognitive and neuroimaging outcomes in treated YWH, compared to controls, in the context of no cannabis use will be ameliorated by mild to moderate cannabis use, while high cannabis use frequency will be associated with worse outcomes in both groups. Of importance, fully understanding the interplay of HIV and cannabis may require consideration of lifetime experiences of adversity. Strong evidence shows that exposure to adverse circumstances, such as maltreatment, violence, and stress, can alter immune and CNS systems, and such exposure is common among YWH and comparable seronegative risk groups. We will assess the influence of cumulative adversity in mediating effects of cannabis and HIV. The proposed study will determine the interactive effects of HIV, cannabis and cumulative adversity on CNS structure and function in 75 YWH (age 18-24) and 75 comparable controls. We will use innovative neuroimaging approaches (MEG to measure functional activity and advanced diffusion approaches), along with brain structure and metabolism and neurocognitive assessment. We will examine mediation of HIV, cannabis and cumulative adversity interactions by inflammation and immune activation, assessed using plasma biomarkers. Examining the interplay of these influences on CNS function and structure will be facilitated by careful characterization of substance use, assessment of cumulative adversity burden rather than single traumatic events, and advanced statistical techniques. Thus, we will examine interactive HIV and cannabis effects on key brain systems; model underlying mechanisms; and examine an important yet understudied influence, cumulative adversity. The study has potential for high impact by improving detection of HIV’s CNS effects and our understanding of pathogenesis. It would enable better prevention of CNS decline, institution of CNS-targeted treatments and cure strategies, and in general mitigation of the CNS impact of HIV for individuals who are early in infection and still in the midst of neurodevelopment where early detection may have the greatest benefit.