Addressing the Syndemic in Indian Country through Integrated, Multi-Level Initiatives Engaging Youth, 2SLGBTQ People, Tribal Epicenters and Health Boards, and Healthcare Providers Via National Network - The Northwest Portland Area Indian Health Board (NPAIHB), established in 1972 by the 43 federally-recognized tribes of Idaho, Oregon, and Washington, works to eliminate health disparities and improve the quality of life of American Indian and Alaska Native (AI/AN) people. Through over 50 years of collaboration with Northwest tribes, states, federal agencies, and community partners on AI/AN health research, surveillance, and policy change, NPAIHB supports and leads efforts to improve the capacity of IHS, Tribal, and Urban (I/T/U) health facilities across the U.S. to carry out core strategies to end the HIV/hepatitis C (HCV)/syphilis epidemics (the syndemic) in their communities. Guided by The Indigenous HIV/AIDS Syndemic Strategy, NPAIHB promotes a broad array of interventions, centering a holistic perspective that aligns with the communities’ needs, and honors the principle of Indigenous Sovereignty. NPAIHB plans to address the syndemic across Indian Country via the following initiatives: 1. National Youth Engagement in HIV/HCV/Sexually Transmitted Infection (STI) Health Resources, Community Engagement and Capacity Building, via supporting NPAIHB’s existing programs, including WeRNative, Healthy Native Youth, and Project Red Talon Network, and through launching and coordinating a new National Youth Engagement Network: This Network will design and disseminate culturally-relevant HIV/HCV/STI health resources for: 1) AI/AN teens/young adults; 2) the community partners and caring adults who support them; and 3) other grantees, to build organizational capacity nationwide. 2. National Two-Spirit/Lesbian, Gay, Bisexual, Transgender, Queer (2SLGBTQ+) Community Engagement, Advocacy, Capacity Development, and Formative Evaluation via NPAIHB’s Paths ReMembered program. Paths ReMembered increases access to affirming healthcare, including HIV PrEP, DoxyPEP, HIV diagnosis and care, Mpox prevention, and other preventative sexual healthcare, for AI/AN 2SLGBTQ+ people by addressing stigma and discrimination that affects them in healthcare settings; educating 2SLGBTQ+ clinicians on the protective effects of Indigenous-specific sexual orientation and gender identities, and access to land, culture, language, ceremony, and Indigiqueer community; and empowering Indigenous 2SLGBTQ+ people by providing information about Indigiqueer traditions. 3. Regional and National Tribal Epicenters/Health Boards/Urban Indian Health Programs via NPAIHB’s Syndemic Support program: The National Center for Syndemic Clinical Support works to improve health systems and epidemiologic/clinical capacity around syndemic preparedness and response within I/T/U settings and increase access and uptake to sexual health education and testing within the Northwest and across Indian Country. The program oversees several projects that support the prevention, diagnosis, and treatment of syndemic-related conditions, including the Native Health Resources website (nativehealthresources.com), an online portal for Indigenized health education materials, comprehensive syndemic facility assessments that support local syndemic preparedness and response, and sexual health campaign development/dissemination. 4. National Extensions for Community Health Outcomes (ECHO) via NPAIHB’s Indian Country ECHO program: Indian Country ECHO is transforming healthcare in Indian Country by increasing access to specialty treatment in reservation/rural/underserved areas. Indian Country ECHO provides frontline healthcare providers with the knowledge and support they need to manage patients with, and prevent complex conditions like, HIV, HCV, substance use disorders, STIs, and others. The national program engages healthcare providers in a continuous learning system and partnering with specialist mentors at an academic medical center or hub. Through these multi-level approaches, which are needed in rural, resource-limited AI/AN settings, NPAIHB will continue to address the syndemic across Indian Country.