Background: Despite high morbidity and mortality among people who use drugs (PWUD) in rural America, most research is conducted within urban areas. We describe influencing factors, motivations, and barriers to research participation and retention among rural PWUD. Methods: We recruited 255 eligible participants from community outreach and community-based, epidemiologic research cohorts from April-July 2019 to participate in a descriptive cross-sectional study. Eligible participants reported opioid or injection drug use to get high within 30 days and resided in high-needs rural counties in Oregon, Kentucky, and Ohio. We aggregated response rankings to identify salient influences, motivations, and barriers. We estimated prevalence ratios to assess for gender, preferred drug use, and geographic differences using log-binomial models.Results: Most participants were male (55%) and recently injected methamphetamine (61%) and/or heroin (57%). The primary influential factors for research participation are confidentiality, amount of financial compensation, and time required. Primary motivations for participation include financial compensation, free HIV/HCV testing, and linkage with resources. Changed or false participant contact information and transportation are principal barriers to retention. Respondents who prefer methamphetamines over heroin are more influenced by why their information is collected and how it is used (PR=1.12; 95%CI:1.00, 1.26). Knowing and wanting to help the research team are motivations for participation among Oregon participants (PR=2.12; 95%CI:1.51, 2.99) and females (PR=1.57; 95%CI:1.09, 2.26).Conclusions: Beyond financial compensation, researchers should emphasize confidentiality, offer testing and linkage with care, use several contact methods, aid transportation, and accommodate demographic differences to improve research participation and retention among rural PWUD.
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