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

项目总结/摘要 考虑到艾滋病毒和艾滋病毒风险与药物使用的重叠，以及艾滋病毒和艾滋病毒感染的共同作用， 和物质使用的慢性炎症，强大的，客观的指标，以定量的类型，数量， 药物使用模式是必要的。自我报告的指标受到社会期望偏差的限制，其中 个体报告提供者或研究者所期望的行为，以及回忆偏差，特别是使用 改变记忆的物质UCSF头发分析实验室（HAL）参与了开发 20年来艾滋病毒领域的客观依从性指标，显示了分析抗逆转录病毒药物的实用性 头发样本中的抗逆转录病毒治疗（ART）水平，以评估ART和暴露前预防（PrEP）依从性， exposure. UCSF HAL还开发了抗结核（TB）药物的头发措施。鉴于关键的 准确评估物质使用的重要性，以及物质对艾滋病毒结果的影响，包括 本提案旨在将我们实验室的技术专长引导到物质使用领域， 监测. 虽然可作为定性（是/否）指标用于法医学，但评估定量使用的毛发水平 多种物质尚未广泛用于物质使用-HIV研究。多物质使用是 通用和定量的多分析物指标允许对依从性和全身炎症的影响 评估。利用一项重要的NIDA资助的队列研究，调查那些患有或处于 艾滋病毒的风险（mSTUDY队列），该提案旨在开发一套毛发检测方法，用于检测 UCSF HAL为NIH资助的研究调查物质使用，HIV和炎症 多分析物面板可同时测量物质（例如甲基苯丙胺、不同的阿片类药物、可卡因 大麻、烟草和其他）将允许对有意或无意的多种物质使用进行量化。 自2013年以来，mSTUDY已经招募了一个生物行为队列，其中包括500多名与男性发生性关系的年轻男性。 男性（男男性行为者）的颜色，一半的积极物质使用者（279和278没有艾滋病毒）在洛杉矶。鲁棒 mSTUDY的标本生物储存库包含76，000个生物样本，其中319个样本中有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 大麻毛发样本采集于2014年8月开始，目前正在进行中。这些头发样本将作为 开发和验证方法的基础上，在头发中的物质的多分析物面板 UCSF HAL（目标1）;分析毛发水平与自我报告的依从性指标之间的关系， 尿液毒理学筛查和临床结果（目标2）;以及评估毛发水平（ 单一或多种物质）和炎症生物标志物（目标3）。通过这项提议，UCSF HAL 旨在成为提供物质使用定量客观指标的参考实验室 在多项研究中，研究了药物使用与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.