Comprehensive High-Impact HIV Prevention Program - San Francisco AIDS Foundation (SFAF) has developed a cutting edge HIV and biomedical prevention service infrastructure through 38 years of effective and proven interventions. This advanced system is led by a clinical care team of knowledgeable pre-exposure prophylaxis (PrEP) and HIV navigators and providers who guide individuals through a continuum of services including comprehensive HIV, STI, and HCV testing, immediate PrEP access, rapid antiretroviral therapy (ART), post-exposure prophylaxis (PEP), public benefits and payment assistance programs, substance use counseling, and behavioral health interventions and social support services that build community and decrease isolation. The SFAF navigation team extends a combination of prevention services to individuals, regardless of HIV status, decreasing HIV transmission. Internal services include HIV prevention education, PrEP/PEP, and syringe access services. Navigators have extensive familiarity with services offered by external trusted partners as well. SFAF navigators guide clients through barriers to HIV care such as insurance, immigration status, food insecurity, medical, and housing needs. SFAF is one of the most respected AIDS service organizations in the United States, serving an estimated 25,000 clients annually through its prevention, treatment, and behavioral health programming. SFAF reaches more than 3,500,000 people annually via public education efforts. Building on its history of programmatic excellence, SFAF is requesting $3,000,000 over five years in partnership with the Center for Disease Control (CDC) to serve two geographic areas hardest hit by HIV in California: (1) Black, Indigenous, and People of Color (BIPOC) persons who inject drugs (PWID), Black/African American men who have sex with men (MSM), and Latinx MSM in the Bay Area and (2) Latinx, MSM, youth and rural workers in the Central Valley. SFAF will implement two comprehensive approaches tailored to each geographic area to increase awareness of HIV status while reaching 2,000 individuals annually from BIPOC communities. SFAF services are conducted in San Francisco across three physical locations in the Mid-Market, South of Market, and Castro neighborhoods, as well as through a Mobile Testing Unit and syringe access and harm reduction mobile efforts in the Tenderloin, Mission, and Bayview neighborhoods. SFAF mobile testing efforts include HIV, STI, and HCV testing, PrEP and HIV navigation, substance health resources, and harm reduction supplies. Combined mobile testing and on-site testing conducted across these locations will enable SFAF to reach 1,500 BIPOC PWID and BIPOC MSM individuals. SFAF will extend an existing at-home-by-mail testing program to targeted Latinx MSM and youth (age 18+) in Fresno county. This innovative online program will include SFAF telehealth HIV clinical services, telePrEP distribution, and HIV navigation in partnership with Fresno Barrios Unidos (FBU). Fresno County possesses very few HIV services and no access to PrEP. At-home-testing, telehealth, and telePrEP will enable SFAF to reach 500 additional Latinx MSM and youth clients in Fresno County to meet the needs of this community. This pilot will expand to reach more residents in California’s Central Valley in the future. Services in this proposal will include immediate connection to PrEP, PEP, and rapid ART. The COVID-19 pandemic has amplified the urgency with which HIV/AIDS organizations address health disparities impacting BIPOC communities, including BIPOC PWID. One strategy for actualizing this includes leveraging SFAF’s infrastructure to support trusted partners that reach priority communities. SFAF’s commitment to health justice supports the CDC’s focus on eliminating health disparities in communities disproportionately affected by HIV. The innovative approaches promoted in this proposal will dramatically advance Ending the Epidemics indicators toward decreased HIV transmission in Bay Area and Fresno communities.