Consequences of marijuana use on inflammatory pathways in HIV-infected youth

艾滋病毒感染者中增长最快的年龄组是19至24岁的青年 占美国新增病例的25%以上长期使用大麻是许多年轻人生活中的毒品选择 艾滋病（HIV）人们对大麻的作用知之甚少，大麻经常与 烟草制品对整体健康的影响。新的治疗指南导致大多数YLWH在开始治疗之前 CD 4 T细胞下降。然而，早期治疗未能逆转艾滋病毒的长期炎症并发症， 介导的巨噬细胞活化。没有基于证据的评估如何娱乐使用 大麻影响了YLWH中的促炎途径。这项研究的目的是确定潜在的 健康益处和/或风险与自我管理的大麻。研究的意义在于 随着娱乐用大麻合法化的增加，这种情况更加严重。长期目标是发现 这些证据为理解大麻在癌症中复杂的、有时相互冲突的作用提供了基础。 免疫调节制定了两个相互关联的具体目标： 目标1.为了确定由娱乐性大麻干扰的炎症免疫途径， 通过应用深度测序方法确定总体转录组， 来自HIV感染者的外周血细胞。 目标二。开发与受干扰的促炎或抗炎途径相关的生物标志物谱 大麻，并发现与受大麻影响的神经认知障碍相关的生物标志物特征， YLWH的娱乐性大麻和烟草使用。 建议的研究重点是参加青少年试验网络纵向研究的YLWH 方案以及从北方大学招募的YLWH前瞻性招募人群 卡罗莱纳。纵向和横向血液样本，临床，人口统计学，行为，[包括 物质使用和频率]，以及神经认知数据将从CD 4 T前治疗的YLWH中进行评估 细胞衰退与会者反映了受艾滋病毒感染影响最大的关键人群，主要是少数民族男子 与18至24岁的男性发生性关系的女性未感染艾滋病毒青年的比较队列 包括年龄、种族和性别的平衡。调查人员包括一个跨学科的团队， 在艾滋病毒感染、免疫、青少年医学、神经认知功能、物质 使用、生物统计学和生物信息学。结果将定义大麻使用对分子的影响 慢性巨噬细胞激活的机制在YLWH谁做，或不，从事物质使用。 拟议的项目目标都是艾滋病毒的高优先级研究领域，特别是其重点使用系统生物学 使用滥用物质的YLWH中免疫激活和炎症的方法。

The most rapidly expanding age group of HIV-infected individuals are youth between the ages of 19 and 24 with more than 25% of new U.S. cases. Recreational marijuana use is the drug of choice by many youth living with HIV [YLWH]. Little is known about the effect of marijuana, which is regularly used in combination with tobacco products, on overall health. New treatment guidelines result in most YLWH initiating therapy before CD4 T cell decline. However, early treatment fails to reverse the long term inflammatory complications of HIV- mediated macrophage activation. There are no evidenced-based assessments of how the recreational use of marijuana impacts pro-inflammatory pathways in YLWH. The goals of the study are to define the potential health benefits and/or risks associated with self-administered marijuana. The significance of the study is accentuated by the increasing legalization of marijuana for recreation use. The long term goal is to discover evidence that provides the basis for understanding the complex and at times conflicting roles for marijuana in immune modulation. Two interconnected specific aims are designed: Aim 1. To identify inflammatory immune pathways perturbed by recreational marijuana with or without concomitant use of tobacco products by applying a deep sequencing approach to define global transcriptome of peripheral blood cells from HIV-infected virally suppressed youth. Aim 2. To develop biomarker profiles associated with pro- or anti-inflammatory pathways perturbed by marijuana and to discover biomarker profiles linked to neurocognitive impairment that are impacted by recreational marijuana and tobacco use by YLWH. Proposed study focus on YLWH who were enrolled in longitudinal studies in the Adolescent Trials Network Protocols as well as a prospectively enrolled population of YLWH recruited from the University of North Carolina. Longitudinal and cross sectional blood samples, clinical, demographic, behavioral, [including substance use and frequency], and neurocognitive data will be evaluated from YLWH treated before CD4 T cell decline. The participants reflect a key populations most impacted by HIV-infection, primarily minority men who have sex with men between the ages of 18 and 24 years. A comparative cohort of HIV-uninfected youth balanced for age, ethnicity, and gender is included. The investigators include an interdisciplinary team with considerable expertise in HIV infection, immunity, adolescent medicine, neurocognitive function, substance use, biostatistics, and bioinformatics. Results will define marijuana use consequences on molecular mechanisms of chronic macrophage activation in YLWH who do, or do not, engage in substance use. Proposed project aims are all high priority research areas in HIV, in particular its focus uses a systems biology approach to immune activation and inflammation in YLWH who use substances of abuse.