Abstract The US strategy to End the HIV Epidemic calls for expanded prevention of new infections and more effective responses to HIV outbreaks. These outbreaks often occur in counties and states that share a disproportional burden of HIV, but the co-occurring and syndemic nature with opioid use disorder (OUD) leaves hundreds of additional counties and regions highly susceptible to new HIV (and HCV) outbreaks. West Virginia (WV) is one such mostly rural setting with an explosive opioid epidemic manifest by the highest per capita rate of overdoses and 5 counties with recent HIV outbreaks. Evidence-based practices to prevent and control HIV in clinical settings include medications for OUD (MOUD), ART treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP). Treatment with these medications, however, first requires screening and evaluation, followed by treatment (SET). Adoption of SET processes may in turn translate to better health outcomes if adequately facilitated. Most rural settings are poorly equipped to provide specialty HIV/HCV/OUD services – an important lesson from Scott County, Indiana. Yet rural settings rely mostly on primary care clinics (PCC) with inadequate expertise to provide these services. To overcome adoption barriers of SET processes for HIV/HCV/OUD, effective facilitation is key and the NIATx treatment improvement strategy combined with ongoing clinical education and support provided by Project ECHO has the potential to increase adoption to integrate specialty HIV/HCV/OUD services into PCCs. Using the i-PARiHS implementation framework, we propose to address this unmet need by first identifying barriers to adoption and scale-up of HIV/HCV/OUD services. Then we will facilitate practice transformation by integrating clinical prompts in the electronic health record (EHR) to screen for HIV/HCV/OUD, followed by treatment prompts. Treatment will be supported by Project ECHO that provides ongoing clinical support to inspire confidence in treatment, alongside a clinical dashboard embedded within the EHR as part of the quality performance improvement activities to sustain integrating HIV/HCV/OUD services into PCCs. We then propose to conduct a stepped wedge, Type 3, hybrid implementation trial to assess the extent to which clinicians adopt and sustain SET processes to integrate care at 20 PCCs that is facilitated by rapid cycle change projects using NIATx. Adoption of SET processes are the primary outcome and a composite quality health indicator (QHI) that combines QHIs for primary care, HIV, HCV and MOUD are secondary efficacy outcomes. Organizational and clinician factors, along with engagement in facilitation activities (NIATx, ECHO sessions) will be explored as potential mediators and moderators. Significance is high for the rural WV context where a volatile opioid epidemic has ignited HIV/HCV outbreaks. Innovation is high by integrating HIV/HCV/OUD services into PCCs using a framework and strategy we successfully used in u...