Unraveling the intersection of substance use, inflammation, and HIV via hair levels

项目摘要/摘要 考虑到艾滋病毒和艾滋病毒风险与药物使用和两者的贡献的重叠综合体 和物质使用到慢性炎症，稳健、客观的衡量标准，以量化类型、数量和 物质使用的模式是必要的。自我报告的指标受到社会期望偏差的限制，其中 个人报告提供者或研究人员想要的行为，并回忆偏见，特别是在使用 改变记忆的物质。加州大学旧金山分校毛发分析实验室(HAL)参与了 目的研究HIV领域20年来的依从性指标，显示分析抗逆转录病毒药物的有效性 头发样本中的治疗(ART)水平评估ART和暴露前预防(PrEP)的依从性和 曝光。加州大学旧金山分校的HAL还开发了抗结核病药物的头发措施。鉴于危急关头 准确评估物质使用情况的重要性，以及物质对艾滋病毒结果的影响，包括 炎症，这项建议旨在将我们实验室的技术专长引导到物质使用领域 监控。 虽然可作为定性(是/否)指标用于取证，但头发水平评估定量使用 多种物质尚未广泛用于物质使用-艾滋病毒研究。多物质的使用是 通用和定量的多分析指标允许对依从性和系统性炎症的影响 评估过了。利用NIDA资助的一项重要的队列研究，调查患有或患有药物的人的药物使用情况 艾滋病毒风险(mSTUDY队列)，这项建议旨在开发一套头发分析方法，用于检测人体内的物质 加州大学旧金山分校HAL用于NIH资助的研究，调查物质使用、艾滋病毒和炎症 用于同时测定物质(如甲基苯丙胺、不同鸦片类药物、可卡因、 大麻、烟草等)将使有意或无意的多物质使用得以量化。 自2013年以来，mSTUDY招募了500多名与男性发生性关系的年轻男性的生物行为队列 有色人种男性(MSM)，洛杉矶一半的活性物质使用者(279人感染艾滋病毒，278人没有感染艾滋病毒)。健壮的 MSTUDY标本生物库包含76,000个生物样本，其中包括来自319个国家的1115个头发样本 报告使用甲基苯丙胺、摇头丸、可卡因、海洛因、芬太尼和/或 大麻。头发样本采集于2014年8月启动，目前仍在进行中。这些头发样本将作为 开发和验证头发中物质的多分析小组方法的基础是 加州大学旧金山分校HAL(目标1)；分析头发水平与自我报告的遵守措施之间的关系， 尿毒学筛查和临床结果(目标2)；以及评估头发水平之间的关系( 单一或多种物质)和炎症生物标志物(目标3)。通过这项提案，加州大学旧金山分校的HAL 旨在成为提供物质使用的定量、客观衡量标准的参考实验室 在头发样本中暴露，用于多项研究，以检查物质使用和艾滋病毒之间的相互作用。

PROJECT SUMMARY/ ABSTRACT Given the overlapping syndemics of HIV and HIV risk with substance use and the contribution of both HIV and substance use to chronic inflammation, robust, objective metrics to quantitate the type, amount, and patterns of substance use are needed. Self‐reported metrics are limited by social desirability bias, where individuals report behavior desired by the provider or researcher, and recall bias, especially with the use of memory‐altering substances. The UCSF Hair Analytical Laboratory (HAL) has been involved in developing objective adherence metrics in the field of HIV for 20 years, showing the utility of analyzing antiretroviral treatment (ART) levels in hair samples to assess ART and pre‐exposure prophylaxis (PrEP) adherence and exposure. The UCSF HAL has also developed hair measures of anti‐tuberculosis (TB) drugs. Given the critical importance of assessing substance use accurately, and the impact of substances on HIV outcomes, including inflammation, this proposal aims to direct our laboratory's technical expertise to the field of substance use monitoring. Although available for forensics as qualitative (yes/no) metrics, hair levels assessing quantitative use of multiple substances have not been widely available for substance use‐HIV studies. Polysubstance use is common and quantitative multi‐analyte metrics allow impacts on adherence and systemic inflammation to be assessed. Harnessing an important NIDA‐funded cohort study investigating substance use in those with or at risk of HIV (the mSTUDY cohort), this proposal aims to develop a suite of hair assays for substances in the UCSF HAL for NIH‐funded research studies investigating substance use, HIV, and inflammation A single muti‐analyte panel to simultaneously measure substances (e.g. methamphetamines, different opiates, cocaine, cannabis, tobacco, and others) will allow intentional or unintentional polysubstance use to be quantitated. The mSTUDY has enrolled a biobehavioral cohort since 2013 of over 500 young men who have sex with men (MSM) of color, half as active substance users (279 with and 278 without HIV) in Los Angeles. The robust specimen biorepository of mSTUDY contains 76,000 biological samples, with 1115 hair samples from 319 mSTUDY participants who report use of methamphetamine, ecstasy, cocaine, heroin, fentanyl, and/or cannabis. Hair sample collection was initiated in August 2014 and is ongoing. These hair samples will serve as the basis of developing and validating the methods for a multi‐analyte panel of substances in hair in the UCSF HAL (Aim 1); analyzing the relationship between hair levels and self‐reported adherence measures, urine toxicology screens, and clinical outcomes (Aim 2); and assessing the relationship between hair levels (of single or multiple substances) and biomarkers of inflammation (Aim 3). Via this proposal, the UCSF HAL aims to become the reference laboratory to provide quantitative, objective metrics of substance use exposure in hair samples for multiple studies examining the interaction between substance use and HIV.