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

总结 这一LITE-2（RFA-AI-21-018）举措是为了应对在阿富汗重新流行的甲基苯丙胺（冰毒）使用， 性少数男性（SMM），这是艾滋病毒发病率的主要驱动因素。总体目标有两个方面： 1)确定吸毒SMM中HIV血清转化风险扩大的多水平和生物行为决定因素; 测试远程保健动机增强干预措施对优化进入或再进入的有效性 在PrEP护理中使用冰毒的SMM患者。来自我们的LITE-1队列的发现（UG 3/UH 3 AI-133675， RFA-AI-16-031）和其他人提供了令人信服的证据，表明冰毒的使用正在增加， 少数种族/族裔，占SMM新感染艾滋病毒的三分之一。根据LITE-2（RFA- AI-21-018）我们提出了一个多组件的倡议，集中在“在哪里”，“如何”和“为什么”使用冰毒 艾滋病风险。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，这是SMM的高优先级人群， 用冰毒吗原因：冰毒是否通过增强直肠免疫失调来放大HIV的生物风险？目标1： 研究艾滋病毒血清转换风险扩大的多层次结构、心理和社会决定因素， 吸食冰毒的人。我们LITE-2计划的核心是一个新的前瞻性生物行为队列， N= 5，000 SMM（n= 3，000 SMM使用冰毒，n= 2，000不使用）。参与者将完成评估， 36个月，并提供生物样本，用于艾滋病毒检测，药物毒理学检测，直肠性传播感染， 细胞因子/趋化因子。我们的主要目标是调查地理空间决定因素的作用（例如， 背景方法和艾滋病毒流行率，城市化）和其他结构性决定因素（例如，结构性柱头 政策/法律所证明的性少数群体）与使用冰毒与艾滋病毒扩增之间的联系 血清转化风险。目的2：测试远程医疗激励的比较和组合效果 优化PrEP使用的强化干预措施。PrEP准备干预支持动机 （PRISM）是一项混合I型、改良析因随机对照试验（RCT），提供远程医疗CM， 激励填写PrEP处方，和2个会话远程医疗MI干预，我们适应了甲基- 使用SMM（R34-DA 046367，Carrico/Grov）。PRISM将招募840名目前未服用 来自LITE-2队列（目标1）的PrEP，以检查CM（n = 280）、MI（n = 280）和MI+CM（n = 280）的有效性 = 280）的主要结果-填写PrEP处方。目的3：确定直肠免疫是否 失调部分解释了使用冰毒的SMM中艾滋病毒血清转化的风险放大。使用病例队列 设计，我们将比较HIV血清转换者（n=450）与匹配的血清阴性对照（n=450），以检查 甲硫氨酸诱导的直肠细胞因子改变与HIV血清转换的临床相关性。这 LITE-2倡议可以通过用SMM改变艾滋病毒预防产生特殊的影响。

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.