Trajectories of socially regulated gene expression, methamphetamine use, and viral load among HIV-positive men who have sex with men (MSM) receiving contingency management

接受应急管理的男男性行为艾滋病毒阳性男性 (MSM) 中社会调节基因表达、甲基苯丙胺使用和病毒载量的轨迹

• 批准号: 10161548
• 负责人: Michael Jonathan Li
• 金额: $ 18.94万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10161548
• 关键词: Abstinence; Addictive Behavior; Address; Adherence; Alcohols; Antibodies; Antiviral Response; Anxiety; Area; Assessment tool; Basic Science; Behavior; Behavioral; Behavioral Sciences; Biological; Biological Assay; Biological Markers; Biological Process; Cardiovascular Diseases; Caring; Chronic; Chronic Disease; Clinical; Clinical Trials; Clinical Trials Design; Compulsive Behavior; Conflict (Psychology); Data Analyses; Development; Dimensions; Discrimination; Disease; Disease Progression; Distress; Drug Addiction; Employment; Ethics; Family; Feeling; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Goals; HIV; HIV Seropositivity; Health; Individual; Inflammation; Inflammatory; Influentials; Interferon Type I; Interferons; Intervention; Investigation; Learning; Legal; Link; Measurement; Measures; Mediating; Medical; Medicine; Mental Depression; Mentored Research Scientist Development Award; Mentors; Mentorship; Methamphetamine; Methods; Outcome; Pathogenesis; Patient Self-Report; Patients; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Play; Population; Prevention; Recovery; Regulator Genes; Regulatory Pathway; Research; Research Personnel; Research Project Grants; Research Training; Role; Severities; Statistical Methods; Stress; Teacher Professional Development; Testing; Training; Training Activity; Treatment Efficacy; Treatment outcome; Urine; Violence; Viral; Viral Load result; addiction; analytical method; antiretroviral therapy; arm; base; biobehavior; career; clinically significant; comorbidity; contingency management; cultural competence; disorder risk; drug testing; emotional distress; experience; high risk; immune function; improved; indexing; insight; men who have sex with men; methamphetamine use; operation; primary outcome; procedure safety; psychologic; psychosocial; relating to nervous system; response; satisfaction; social; social genomics; substance use; substance use treatment; success; therapy adherence; transcriptomics; transmission process

PROJECT ABSTRACT The K01 Mentored Research Scientist Development Award will provide Dr. Michael Li with invaluable research experience, mentored training from interdisciplinary faculty, and training activities in a combination of behavioral and basic sciences, which will prepare him well in his career as a biobehavioral researcher in addiction medicine and HIV treatment/prevention. This K01 mechanism will support Dr. Li’s research and training efforts to develop expertise in the following areas: (1) neurally regulated “stress” gene expression markers and links to addiction and HIV disease progression; (2) cultural competence and ethical conduct; (3) technical assay and substantive analytic methods in gene expression research; (4) clinical trial methods; and (5) professional development. Dr. Li has assembled an interdisciplinary mentorship team who will support key aspects of his training and research. Dr. Steven Shoptaw is a highly productive and influential researcher in addiction medicine, and he has an extensive track-record mentoring people who later became successful independent researchers. Co-mentor Dr. Steven Cole has pioneered the field of social genomics, and will direct Dr. Li’s training in transcriptomic methods. Dr. Jesse Clark will guide Dr. Li in clinical trial operations and safety procedures, and Dr. Thomas Belin will provide extensive mentoring in advanced statistical methods and inferential frameworks in clinical trials. Dr. Li proposes to investigate whether a neurally regulated “stress” gene expression pattern can serve as a clinically meaningful, non-abstinence-based endpoint for contingency management for methamphetamine (METH) use disorder (MUD) in MSM living with HIV. Abstinence determined by urine testing has been the only standard clinical outcome for MUD treatment, but provides an incomplete picture of patient recovery. The gene expression pattern called the conserved transcription response to adversity (CTRA) may provide insight into changes in both psychosocial health and pathogenesis over the course of MUD treatment. The CTRA is marked by upregulated expression of pro-inflammatory genes and downregulated expression of Type I interferon genes in response to negative psychosocial experiences such as depression, anxiety, and violence, problems also comorbid with METH use. The CTRA also involves some of same gene regulatory pathways that contribute to METH-related pathogenesis, such as those involving inflammation and innate antiviral responses (relevant to PLWH). My proposed research will use a two-arm clinical trial design (N=55) with 35 HIV-positive MSM with MUD receiving contingency management for METH reduction, and 20 HIV-positive MSM who qualify as a non-substance-using control to accomplish the following aims: 1) to investigate whether CTRA gene expression coincides with METH use and viral load; 2) to investigate whether psychosocial indicators of addiction are associated with CTRA; and 3) to conduct an exploratory pilot investigation to determine the degree to which CTRA mediates the association between METH use and viral load. Together, this K01 research project and training plan will play a fundamental role in my early success as an independent substance use and HIV researcher.

项目摘要 K01指导研究科学家发展奖将为Michael Li博士提供宝贵的研究 经验，跨学科教师的指导培训以及行为相结合的培训活动 和基础科学，这将使他在成瘾医学领域的生物行为研究人员的职业生涯中做好很好的准备 和HIV治疗/预防。这种K01机制将支持Li博士的研究和培训工作以发展 以下领域的专业知识：（1）神经调节的“压力”基因表达标记和与成瘾的联系 和艾滋病毒疾病进展； （2）文化能力和道德行为； （3）技术评估和实质性 基因表达研究中的分析方法； （4）临床试验方法； （5）专业发展。博士 李已经组建了一个跨学科的心态团队，该团队将支持他的培训和研究的关键方面。 Steven Shoptaw博士是成瘾医学领域高效且有影响力的研究人员，他有一个 后来成为成功的独立研究人员的广泛的田径指导者。联合主管博士 史蒂文·科尔（Steven Cole）开创了社会基因组学领域，并将指导李博士在转录组方法中的培训。 杰西·克拉克（Jesse Clark）博士将指导Li博士在临床试验和安全程序中 在临床试验中提供高级统计方法和推论框架的广泛心理。李博士 提出研究神经调节的“胁迫”基因表达模式是否可以用作临床 甲基苯丙胺（甲基苯丙胺）使用的有意义的，非固定的终点 患有艾滋病毒的MSM中的疾病（泥）。通过尿液测试确定的禁欲是唯一的标准 泥处理的临床结果，但提供了患者康复的不完整情况。基因表达 称为广告（CTRA）的保守转录响应的模式可以洞悉两者的变化 在整个泥处理过程中，社会心理健康和发病机理。 CTRA的标记已更新 促炎基因的表达和I型干扰素基因的下调表达响应于 抑郁症，动画和暴力等负面的社会心理经历，问题也与 使用甲基。 CTRA还涉及一些相同的基因调节途径，这些途径有助于Meth相关 发病机理，例如涉及炎症和先天抗病毒反应的发病机理（与PLWH有关）。我的 拟议的研究将使用带有35个HIV阳性MSM的两臂临床试验设计（n = 55），并接受泥浆接收 减少甲基甲基甲基的应急管理和20个艾滋病毒阳性MSM，他们有资格成为非替代品的使用 控制以下目标：1）研究CTRA基因表达是否与甲基相一致 使用和病毒载荷； 2）研究成瘾的社会心理指标是否与CTRA相关；和 3）进行探索性试点调查，以确定CTRA介导关联的程度 在甲基甲基甲基甲基苯酚和病毒载荷之间。该K01研究项目和培训计划将共同发挥基本 在我作为独立药物使用和艾滋病毒研究人员的早期成功中的作用。