Authors: Eric Romo, Abby E. Rudolph, Thomas J. Stopka, Bo Wang, Bill M. Jesdale, Peter D. Friedmann Background/Objectives: Obtaining sterile syringes via syringe services programs (SSPs) and pharmacies reduces injection-mediated risks associated with hepatitis C virus (HCV), but whether indirect use of SSPs via secondary exchange confers the same benefit remains unknown, particularly in rural settings. We compared HCV serostatus and injection-mediated risks by primary syringe source among a sample of rural people who inject drugs (PWID). Methods: Data are from a cross-sectional study of adult PWID recruited from rural counties in New Hampshire, Vermont, and Massachusetts using respondent-driven sampling between 2018 and 2019. Study staff performed HCV antibody testing. An audio computer-assisted self-interview assessed sociodemographics and past 30-day injection-mediated risks. Based on self-report, participants’ primary syringe source was classified as direct SSP, pharmacy, indirect SSP (secondary exchange), or “other” sources (friend/acquaintance, street seller, partner/relative, found them). Mixed effects modified Poisson models assessed associations between syringe source and HCV seroprevalence and injection-mediated risks. Results: Among 397 PWID, the most common primary syringe source was “other” sources (33%), followed by pharmacies (27%), SSPs (22%), and secondary exchange (18%). In multivariable models, participants primarily obtaining syringes from pharmacies had a lower HCV seroprevalence (adjusted prevalence ratio [APR]:0.85, 95% confidence interval [CI]:0.73-1.00) than participants using other sources. Compared with those primarily using other sources, PWID obtaining syringes directly from SSPs or pharmacies were less likely to report borrowing syringes (APR[SSP]:0.60, 95% CI:0.43-0.85 and APR[Pharmacies]:0.70, 95% CI:0.52-0.93), borrowing injection equipment (APR[SSP]:0.59, 95% CI:0.50-0.69 and APR[Pharmacies]:0.81, 95% CI:0.68-0.98), and backloading (APR[SSP]:0.65, 95% CI:0.48-0.88 and APR[Pharmacies]:0.78, 95% CI:0.67-0.91). Obtaining most syringes via secondary exchange was negatively, but imprecisely, associated with each injection risk behavior (e.g., APR borrowed syringes:0.89, 95% CI:0.62-1.28). Conclusions: PWID in rural New England largely relied on unauthorized syringe sources. Primarily obtaining syringes from an SSP or pharmacy was associated with reductions in injection-mediated risks and decreased HCV seroprevalence, demonstrating the need for expanded local access. Eric Romo MD/PhD Candidate Clinical and Population Health Research Program University of Massachusetts Medical School 406-437-3720 Confidentiality Notice: This e-mail message, including any attachments, is for the sole use of the intended recipient(s) and may contain confidential, proprietary and privileged information. Any unauthorized review, use, disclosure or distribution is prohibited. If you are not the intended recipient, please contact the sender immediately and destroy or permanently delete all copies of the original message