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

艾滋病毒感染人数增长最快的年龄段是19至24岁的年轻人。 超过25%的美国新病例。娱乐性使用大麻是许多年轻人选择的毒品 艾滋病毒携带者[青年会]。人们对大麻的影响知之甚少，大麻经常与大麻联合使用 烟草产品对整体健康的影响。新的治疗指南导致大多数YLWH以前开始治疗 CD4T细胞下降。然而，早期治疗未能扭转艾滋病毒的长期炎性并发症- 介导的巨噬细胞激活。没有任何基于证据的评估来评估娱乐设施的使用 大麻影响YLWH的促炎途径。这项研究的目标是确定潜在的 与自行管理的大麻相关的健康益处和/或风险。这项研究的意义在于 娱乐用大麻的合法化程度越来越高，这一点更加突出。长期目标是发现 为理解大麻复杂且有时相互冲突的角色提供基础的证据 免疫调节。设计了两个相互关联的具体目标： 目的1.确定娱乐性大麻对炎性免疫通路的干扰 通过应用深度测序方法定义整体转录组来同时使用烟草产品 来自感染艾滋病毒的被病毒抑制的年轻人的外周血细胞。 目的2.发展与促炎或抗炎途径相关的生物标志物 并发现与神经认知障碍有关的生物标记物特征。 基督教青年会娱乐用大麻和烟草使用情况。 建议的研究重点是参加青少年试验网络纵向研究的青少年儿童 协议以及从北方大学招募的预期登记的青年妇女会人口 卡罗莱纳。纵向和横断面血样、临床、人口学、行为[包括 物质使用和频率]，神经认知数据将在CD4T之前从YLWH治疗中评估 细胞衰退。参与者反映了受艾滋病毒感染影响最大的关键人群，主要是少数族裔男性 与18至24岁之间的男性发生性关系。未感染艾滋病毒的青年的对照队列 包括了年龄、种族和性别的平衡。调查人员包括一个跨学科团队， 在艾滋病毒感染、免疫、青少年医学、神经认知功能、物质方面拥有丰富的专业知识 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 YLWH中参与或不参与物质使用的慢性巨噬细胞激活机制。 拟议的项目目标都是艾滋病毒的高度优先研究领域，特别是其重点使用系统生物学 YLWH滥用药物者免疫激活及炎症反应的探讨

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.