PROJECT SUMMARY/ABSTRACT We propose to assess the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) of existing and emerging harm reduction services designed to improve the health of people who inject or smoke illicit drugs in San Francisco, California. The major health complications associated with injecting or smoking heroin, fentanyl analogs, methamphetamine, and cocaine include overdoses and viral (e.g., HIV, hepatitis) and bacterial infections (e.g., skin and soft tissue infection and endocarditis). Steep increases in morbidity and mortality associated with drug use have motivated people in community-based organizations to conceptualize and implement innovative harm reduction interventions to thwart these health emergencies. The burgeoning HIV epidemic spawned syringe service programs (SSPs) in the late 1980s. Rising opioid overdose mortality spawned overdose education and naloxone distribution (OEND) in the late 1990s. The recent emergence of fentanyl analogs in the illicit drug market spawned fentanyl test strips (FTS), community-based Fourier-transform infrared spectroscopy drug checking (FTIR), and safe consumption sites (SCS). Now, the re-emergence of methamphetamine has spawned a methamphetamine sobering center opening in San Francisco in 2022. Given the staggered implementation of harm reduction services over the past 35 years, the state of the evidence base varies for each. The RE-AIM implementation science framework helps guide evaluations by considering their Reach, Effectiveness, Adoption, Implementation, and Maintenance. Our aims are as follows: Aim 1: Assess changes in and factors associated with equitable access to an array of harm reduction services for people who inject or smoke illicit drugs in San Francisco over time (Reach). Aim 2: Determine the effectiveness of existing and emerging harm reduction services in reducing drug-related harm among people who inject or smoke illicit drugs in San Francisco (Effectiveness). Aim 3: Explore Adoption, Implementation, and Maintenance of harm reduction services within community- based organizations over time (Adoption, Implementation, and Maintenance). To achieve Aims 1 and 2, we will recruit people who use drugs (PWUD) using targeted sampling into a serial cross-sectional study. In each of 4 years, a new sample (n=800) of PWUD will be recruited and surveys will ascertain access to and use of various existing and emerging harm reduction interventions and drug-related harm. To achieve Aim 3, we will conduct a serial cross-sectional qualitative study of staff (n=30 annually) at all community-based organizations that provide harm reduction services in San Francisco (currently n=10) to assess Adoption, Implementation, and Maintenance. Our proposed study will provide data on access to, implementation of, and impact of emerging and evolving harm reduction interventions designed to reduce drug-related harm, thereby helping US policymakers and service providers move effective services along the continuum toward scaled implementation and maintenance.

PROJECT NARRATIVE Scientific evaluations play an important role in assessing whether emerging and existing harm reduction interventions are not only effective within real-world delivery contexts but also how implementation and equitable access can be improved. Our proposed project will assess the reach, effectiveness, adoption, implementation, and maintenance of six emerging and existing harm reduction services that have been or are about to be implemented in San Francisco, along with any new harm reduction services that emerge during our study period. This is critical as public health agencies, community-based organizations, and policy makers are trying to figure out how to tackle an overwhelming amount of health-related harm among people who use drugs in the United States.