MSM and Substances Cohort at UCLA Linking Infections Noting Effects (MASCULINE)

项目总结/摘要 随着药物治疗的进步，艾滋病毒的治疗和预防方法也在不断演变。然而 在美国，使用药物的主要人群，如与男性发生性关系的有色人种， （MoCSM）面临社会行为障碍，阻碍了整个艾滋病毒护理和预防的获取和遵守 产生HIV相关生物变化的级联。阐明物质使用如何影响基础， 艾滋病毒的生物、行为和社会方面对推进艾滋病毒预防和治疗至关重要。响应 NIDA RFA-DA-18-011 HIV/AIDS和物质使用的队列研究（U 01），洛杉矶加州大学 洛杉矶（加州大学洛杉矶分校）寻求继续在加州大学洛杉矶分校的男男性接触者和物质队列连接感染注意到影响 （MASCULINE或“mSTUDY”），并将其提供的科学机会扩展到另一个 五年我们提议的竞争性更新将维持并动态更新物质使用队列 艾滋病毒血清反应阳性（艾滋病毒+）和艾滋病毒血清反应阴性（艾滋病毒-）的高风险MoCSM退休老年人，不使用药物 增加年轻的物质使用者。如果更新，该队列将继续向我们的 良好的特征，广泛的生物行为知识库，并为高影响力的科学提供平台。 药物使用继续影响对治疗和预防方案的依从性， 流行网络。建议的研究人员领导科学研究药物使用之间的关联， 行为和传染病，并将贡献广泛的跨学科工作组合，从免疫学 以及基础科学到流行病学、预防和治疗。该MoCSM队列将表征：（i）影响 物质使用对获得艾滋病毒和其他性传播感染（性传播感染：淋病，衣原体， （二）在何种程度上物质的使用在MoCSM促进传播艾滋病毒的行为相比， （iii）物质使用和HIV对粘膜环境的影响;（iv） 物质使用对艾滋病毒疾病进展的影响;以及物质使用与艾滋病毒感染之间的相互作用， 炎症反应。我们确定了兴奋剂、大麻和其他物质使用的直接方式， 结合特定的行为可以改变艾滋病毒的传播和发展动力， 通过免疫功能和微生物组来调节隔室。该申请还建议扩大一个已经 强大的生物储存库，可为更广泛的研究社区提供标本。该队列将由 重复数据访问的514名MoCSM。至少有一半将是活跃的物质使用者，年龄在30岁以下。 随着一个完整的入组队列，mSTUDY已经开始产生高影响力的出版物和衍生研究 新整合的大样本数据集的项目。下一个周期将进一步刺激基础和 来自合作研究者的生物创新科学，与其他NIDA新建立的合作 队列，外部资助的科学家和产生高影响力的未来科学。

PROJECT SUMMARY/ABSTRACT HIV treatment and prevention approaches are evolving in response to advancements in pharmacotherapies. Yet in the United States substance using members of key populations such as men of color who have sex with men (MoCSM) face socio-behavioral barriers that inhibit access and adherence across the HIV Care and Prevention Cascades that produce HIV relevant biological changes. Elucidation of how substance use affects basic, biological, behavioral, and social aspects of HIV is vital to advance HIV prevention and treatment. In response to NIDA RFA-DA-18-011 Cohort Studies of HIV/AIDS and Substance Use (U01), the University of California, Los Angeles (UCLA) seeks to continue the MSM and Substances Cohort at UCLA Linking Infections Noting Effects (MASCULINE or the “mSTUDY”) established in 2013 and to extend the scientific opportunities it offers for another five years. Our proposed competitive renewal will sustain and dynamically refresh the cohort of substance-using HIV-seropositive (HIV+) and high-risk HIV-seronegative (HIV-) MoCSM by retiring older, non-substance-using members and adding younger substance-users. If renewed, this cohort will continue to add specimens to our well-characterized, extensive biobehavioral repository and to provide a platform for high-impact science. Substance use continues to effect adherence to treatment and prevention regimens thereby sustaining high prevalence networks. Proposed investigators lead the science on studying associations between drug use, behaviors, and infectious disease and will contribute a broad portfolio of interdisciplinary work from immunology and basic science to epidemiology, prevention and treatment. This cohort of MoCSM will characterize: (i) effects of substance use on acquisition of HIV and other sexually transmitted infections (STIs: gonorrhea, Chlamydia, syphilis); (ii) the extent to which substance use in MoCSM facilitates behaviors that transmit HIV compared to non-drug using MoCSM (iii) the effects of substance use and HIV on the mucosal environment; (iv) effect of substance use on HIV disease progression; and interactions between substance use and HIV infection on the inflammatory response. We identify the direct ways stimulants, cannabis and other substance use in combination with specific behaviors can change HIV transmission and progression dynamics in multiple compartments via immune function and the microbiome. The application also proposes to expand an already robust biorepository with specimens available for the broader research community. This cohort will be comprised of 514 MoCSM with repeated data visits. At least half will be active substance users and younger than age 30. With a fully enrolled cohort, the mSTUDY has begun to produce high impact publications and spinoff research projects with newly integrated datasets of large sample sizes. The next cycle will further stimulate basic and biologically innovative science from collaborating investigators, newly established collaborations with other NIDA cohorts, and externally funded scientists and generate high impact future science.