ABSTRACT In New England’s rural areas, the epidemic of opioid use disorder (OUD) and its related conditions: overdose, HIV, hepatitis C virus (HCV), sexually transmitted infections (STIs) and other infectious comorbidities present the most substantial challenges to public health and health care in decades. The Drug Injection Surveillance and Care Enhancement for Rural Northern New England (DISCERNNE) study examined the epidemiology of opioid use, its infectious consequences, and service accessibility in rural counties along the Interstate 91 corridor in Massachusetts, New Hampshire and Vermont. Our initial work (UG3) found that syringe-sharing and HCV are highly prevalent, while access to clean syringes, phlebotomy services, HCV testing and treatment are limited placing these counties at high risk for a Scott County-like HIV outbreak. Other relevant lessons learned from the UG3 phase include: (1) any intervention must limit the burden on the local harm reduction and medical institutions that have limited space and resources for new programming and are straining to meet their current responsibilities; and (2) any intervention must account for the reluctance of active PWIDs to seek care from a health system that has treated them poorly. In the second phase of the DISCERNNE study (UH3), we are working closely with harm reduction experts in these rural communities to deploy a mobile syringe services van to expand HCV antibody and viral testing, bolster syringe access, and provide HCV telemedicine treatment. Study participants with HCV antibody present will undergo testing for HCV viremia, and, as appropriate, receive initial hepatitis B virus (HBV) and/or hepatitis A virus (HAV) vaccines. Participants (n= 220) are randomized to one of two strategies for HCV treatment: Enhanced Usual Care (EUC) – referral with care navigation to an HCV treatment provider. Mobile tele-HCV Care (MTC) – telemedicine Direct-Acting Antiviral treatment for HCV (DAA) on the van. If effective, this mobile model of HCV telehealth integrated with syringe services will provide a promising approach for local public health authorities seeking to curb opioid injection, syringe sharing and HCV rates in rural America, and reduce the risk environment for HIV outbreaks in those communities. An administrative supplement is requested to offset an increase in project costs and challenges related to the Covid-19 pandemic.