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: 10595088
• 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/10595088
• 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 Progression; Distress; Drug Addiction; Employment; Ethics; Faculty; Family; Feeling; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Goals; HIV; HIV Seropositivity; Health; Individual; Inflammation; Inflammatory; Influentials; Interferon Type I; Intervention; Investigation; Learning; Legal; Link; Measurement; Measures; Mediating; Medical; Medicine; Mental Depression; Mentored Research Scientist Development Award; Mentors; Mentorship; Methamphetamine; Methamphetamine use disorder; Methods; Outcome; Pathogenesis; Patient Self-Report; Patients; Pattern; Personal Satisfaction; Persons; Pharmaceutical Preparations; Physiological; Play; Population; Prevention; Productivity; Qualifying; Recovery; Regulator Genes; Regulatory Pathway; Research; Research Personnel; Research Project Grants; Research Training; Role; Severities; Statistical Methods; Stress; Testing; Training; Training Activity; Treatment Efficacy; Treatment outcome; Urine; Violence; Viral; Viral Load result; addiction; analytical method; antiretroviral therapy; arm; biobehavior; career; clinically significant; comorbidity; contingency management; cultural competence; disorder risk; drug testing; emotional distress; experience; high risk; immune function; improved; indexing; insight; long term recovery; men who have sex with men; methamphetamine use; neural; operation; primary outcome; procedure safety; psychologic; psychosocial; 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李国能博士提供宝贵的研究 经验，来自跨学科教员的指导培训，以及结合行为的培训活动 和基础科学，这将为他作为成瘾医学生物行为研究人员的职业生涯做好准备 和艾滋病毒治疗/预防。这一K01机制将支持李博士的研究和培训努力，以开发 在以下领域有专长：(1)神经调节的“应激”基因表达标记和与成瘾的联系 和艾滋病毒疾病进展；(2)文化能力和道德操守；(3)技术分析和实质性 基因表达研究的分析方法；(4)临床试验方法；(5)专业发展。Dr。 李已经组建了一个跨学科的指导团队，他们将支持他的培训和研究的关键方面。 史蒂文·肖普托博士是一位在成瘾医学领域卓有成效和有影响力的研究人员，他有 广泛的跟踪记录，指导那些后来成为成功的独立研究人员的人。共同导师Dr。 史蒂文·科尔是社会基因组学领域的先驱，他将指导李博士在转录切分方法方面的培训。 杰西·克拉克博士将指导李博士的临床试验操作和安全程序，托马斯·贝林博士将指导 在临床试验中提供先进的统计方法和推理框架方面的广泛指导。李博士 建议研究神经调节的“应激”基因表达模式是否可以作为临床上的 用于甲基苯丙胺(冰毒)使用应急管理的有意义的、非基于戒断的终点 感染艾滋病毒的男男性接触者的精神障碍(MUD)。通过尿检来确定禁欲是唯一的标准 MUD治疗的临床结果，但提供了患者康复的不完整图景。基因表达 被称为保守的逆境转录反应(CTRA)的模式可能提供对两者变化的洞察 泥浆治疗过程中的心理社会健康和发病机制。CTRA被标记为Upregated 促炎症基因的表达和I型干扰素基因的下调 消极的心理社会经历，如抑郁、焦虑和暴力，问题也伴随着 吸食冰毒。CTRA还涉及一些与冰毒相关的基因调控途径 发病机制，如涉及炎症和先天抗病毒反应(与PLWH相关)。我的 建议的研究将采用双臂临床试验设计(N=55)，对象为35名HIV阳性男男性接触者，并接受MUD 减少冰毒的应急管理，以及20名符合非物质使用资格的艾滋病毒阳性男男性行为者 对照以实现以下目的：1)调查CTRA基因表达是否符合冰毒 使用和病毒载量；2)调查成瘾的心理社会指标是否与CTRA有关；以及 3)进行探索性试点调查，以确定CTRA在多大程度上调解该协会 冰毒使用和病毒载量之间的关系。K01研究项目和培训计划的结合将起到基础性的作用 作为一名独立的药物使用和艾滋病毒研究人员，我在早期的成功中扮演了重要角色。