Optimizing HIV prevention for highly vulnerable methamphetamine-using sexual minority men

摘要 这项LITE-2(RFA-AI-21-018)倡议是为了应对#年甲基苯丙胺(冰毒)使用的死灰复燃的流行。 性少数男性(SMM)，这是艾滋病毒发病率的主要驱动因素。总体目标有两个： 1)确定在使用冰毒的SMM中放大的艾滋病毒血清转换风险的多水平和生物行为决定因素； 以及2)测试远程健康动机增强干预对优化进入或重返大气层的有效性 使用冰毒的SMM进入PrEP护理连续体。我们的Lite-1队列(UG3/UH3 AI-133675， RFA-AI-16-031)和其他文件提供了令人信服的证据，表明冰毒的使用正在增加，影响不成比例 种族/少数民族，占SMM新艾滋病毒感染人数的三分之一。响应LITE-2(RFA- AI-21-018)我们提出了一项由多个组成部分组成的倡议，重点关注冰毒在哪里、如何使用和为什么使用 和艾滋病毒风险。地点：冰毒使用与艾滋病毒发病率相关的地理空间决定因素是什么？ 如何：我们如何支持(重新)进入PrEP护理连续体，以及这些高度优先的SMM人群 吸食冰毒？为什么：冰毒通过增强直肠免疫失调而放大艾滋病毒的生物学风险？目标1： 研究放大的HIV血清转换风险的多层次结构、心理和社会决定因素 使用冰毒的SMM。我们的Lite-2计划的核心是一个新的预期生物行为队列 N=5,000名SMM(n=3,000名使用冰毒的SMM，n=2,000名不使用冰毒的SMM)。参与者将完成以下评估 36个月，并为艾滋病毒检测、药物毒理检测、直肠性传播感染和直肠提供生物样本 细胞因子/趋化因子。我们的主要目标将是调查地理空间决定因素(例如， 背景冰毒和艾滋病毒流行率、都市性)和其他结构性决定因素(例如 政策/法律证明的性少数群体)与使用冰毒与放大的艾滋病毒之间的联系 血清转换风险。目标2：检验远程健康激励的比较效果和综合效果 优化PrEP使用的增强干预措施。用于支持动机的准备就绪干预 (PRISM)是一种混合类型的远程健康CM的改良因子随机对照试验(RCT)，它提供了 对填写PrEP处方的激励措施，以及我们用冰毒适应的两个疗程的远程健康MI干预- 使用SMM(R34-DA046367，Carrico/Grov)。PRISM将招收840名目前未服用冰毒的SMM 来自Lite-2队列(目标1)的准备，以检查CM(n=280)、MI(n=280)和MI CM(N)的有效性 =280)对主要结果-填写PrEP处方。目标3：确定更大的直肠免疫 调节失调部分解释了使用冰毒的SMM艾滋病毒血清转换风险放大的原因。使用病例队列 设计，我们将比较HIV血清转换者(n=450)和匹配的血清阴性对照(n=450)以检查 冰毒引起的直肠细胞因子改变与HIV血清转换的临床相关性。这 Lite-2倡议可以通过利用SMM改变艾滋病毒预防工作而产生特殊影响。

SUMMARY This LITE-2 (RFA-AI-21-018) initiative responds to a resurgent epidemic of methamphetamine (meth) use in sexual minority men (SMM), which is a primary driver of HIV incidence. The overarching goals are two-fold: 1) identify multi-level and bio-behavioral determinants of amplified HIV seroconversion risk in meth-using SMM; and 2) test the effectiveness of telehealth motivational enhancement interventions for optimizing entry or re-entry of SMM who use meth into the PrEP care continuum. Findings from our LITE-1 cohort (UG3/UH3 AI-133675, RFA-AI-16-031) and others provide compelling evidence that meth use is increasing, disproportionally impacts racial/ethnic minorities, and accounts for one-in-three new HIV infections in SMM. In response to LITE-2 (RFA- AI-21-018) we propose a multi-component initiative zeroing in on the “Where,” “How,” and “Why” of meth use and HIV risk. Where: What are the geospatial determinants of the association of meth use with HIV incidence? How: How can we support (re-)entry into the PrEP care continuum with this high priority population of SMM who use meth? Why: Does meth amplify biological risk of HIV by potentiating rectal immune dysregulation? Aim 1: Examine multi-level structural, psychological, and social determinants of amplified HIV seroconversion risk in SMM who use meth. The centerpiece of our LITE-2 initiative is a new prospective, bio-behavioral cohort with N=5,000 SMM (n=3,000 SMM who use meth, n=2,000 who do not). Participants will complete assessments over 36 months and provide biological samples for HIV testing, drug toxicology testing, rectal STIs, and rectal cytokines/chemokines. Our primary goal will be to investigate the role of geospatial determinants (e.g., background meth and HIV prevalence, urbanicity) and other structural determinants (e.g., structural stigma of sexual minorities as evidenced by policies/laws) in relation to the association of meth use with amplified HIV seroconversion risk. Aim 2: Test the comparative and combined effectiveness of telehealth motivational enhancement interventions for optimizing PrEP use. PrEP Readiness Interventions for Supporting Motivation (PRISM) is a hybrid type I, modified factorial randomized controlled trial (RCT) of telehealth CM that provides incentives for filling a PrEP prescription, and a 2-session telehealth MI intervention that we adapted with meth- using SMM (R34-DA046367, Carrico/Grov). PRISM will enroll 840 meth-using SMM who are not currently taking PrEP from the LITE-2 cohort (Aim 1) to examine the effectiveness of CM (n = 280), MI (n = 280), and MI+CM (n = 280) on the primary outcome – filling a PrEP prescription. Aim 3: Determine whether greater rectal immune dysregulation partially explains amplified risk of HIV seroconversion in SMM who use meth. Using a case-cohort design, we will compare HIV seroconverters (n=450) with matched seronegative controls (n=450) to examine the clinical relevance of meth-induced alterations in rectal cytokines with respect to HIV seroconversion. This LITE-2 initiative could have an exceptional impact by transforming HIV prevention with SMM.