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

抗逆转录病毒治疗（ART）减轻了但没有消除中枢神经系统（CNS）的影响， 人类免疫缺陷病毒（艾滋病毒）。对认知和大脑完整性的影响现在更微妙，但随着 未知的长期影响，共病的可能性，以缓和，掩盖或改善艾滋病毒 影响越来越重要。年轻人（“青年”）新感染艾滋病毒的比率很高， 未充分研究的具有显著影响HIV CNS表现潜力的常见合并症：大麻 使用和累积的逆境。两者都可能改变免疫功能和炎症，作为其 影响HIV的中枢神经系统的影响，除了他们的独立影响。我们的初步数据显示， 与对照组相比，HIV感染青年（YWH）的认知和神经影像学结果（例如，记忆力差， 执行功能、前额叶皮质变薄、使用脑磁图改变功能激活 [MEG]）被减弱，或者在某些情况下，通过轻度至中度而不是重度使用大麻而逆转。我们 假设与对照组相比，YWH治疗组的认知和神经影像学结果更差， 没有大麻使用的情况将通过轻度至中度大麻使用得到改善， 在两组中，频率与更差的结果相关。重要的是，充分了解 艾滋病毒和大麻的相互作用可能需要考虑到一生的逆境经历。有力证据 表明暴露于不利的环境，如虐待，暴力和压力，可以改变免疫系统， 和中枢神经系统，这种暴露在YWH和类似的血清阴性风险组中很常见。我们 将评估累积逆境在介导大麻和艾滋病毒影响方面的影响。拟定研究 将确定艾滋病毒、大麻和累积逆境对中枢神经系统结构和功能的相互影响 75例YWH（18-24岁）和75例对照组。我们将使用创新的神经影像学方法（MEG， 测量功能活动和高级扩散方法），沿着脑结构和代谢 和神经认知评估我们将研究艾滋病毒，大麻和累积逆境的调解 通过炎症和免疫活化的相互作用，使用血浆生物标志物评估。检查 这些对中枢神经系统功能和结构的影响的相互作用将通过仔细表征 物质使用，评估累积的逆境负担，而不是单一的创伤事件， 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相互作用; 潜在的机制;并检查一个重要的，但研究不足的影响，累积逆境。的 这项研究有可能通过提高对HIV中枢神经系统影响的检测和我们对 发病机制它将能够更好地预防CNS下降，建立CNS靶向治疗， 治愈策略，以及在一般情况下减轻感染早期个体的HIV对CNS的影响 并且仍然处于神经发育的中期，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.