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

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.