Street prep: expanding a low-barrier prep delivery model among people who use drugs and experiencing homelessness in SAN francisco

The National Institute on Drug Abuse awarded Public Health Foundation Enterprises, Inc. (doing business as Heluna Health) $1,177,338 on April 15, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to test and expand the Street Prep intervention, a low-barrier HIV pre-exposure prophylaxis delivery model for people who use drugs and experience homelessness in San Francisco.

The project conducts a Type 2 hybrid effectiveness-implementation randomized trial enrolling 150 participants via respondent-driven sampling from existing cohort studies and social networks of people who use drugs. Participants are randomized to either standard-of-care clinic linkages or the Street Prep intervention, which provides access to a mobile health clinic, tailored navigation addressing HIV prevention and substance use needs, and transportation to low-barrier drop-in clinics for ongoing healthcare. The work responds to a documented public health gap: new HIV diagnoses among people who inject drugs in San Francisco rose 34 percent from 2019 to 2021, while only 1.2 percent of surveyed people who inject drugs had used PrEP in the prior year.

Place of performance is City of Industry, California. The period of performance runs from April 15, 2026, through January 31, 2031.

Abstract

HIV disproportionately impacts people who use drugs while scale up of prevention interventions lag for this population. New HIV diagnoses in SAN francisco among people who inject drugs increased by 34% from 2019 to 2021. Rises in methamphetamine and fentanyl both by injection and non-injection use are associated with new HIV infections. While efforts to address substance use have grown, little has been done to address HIV among people who use drugs. A 2022 survey of people who inject drugs in SAN francisco found that HIV testing went down 30% from the prior 2 years and only 1.2% of participants had used HIV pre-exposure prophylaxis, or prep, in the past year. People who use drugs face unique structural and substance use-related challenges to accessing services, amplifying their vulnerability for HIV and reducing their uptake of prep. In the face of increasing HIV transmission, evidence-based interventions demonstrating successful prep uptake and persistence remain limited, representing a widening GAP in public health. Our team proposes to test the street prep intervention, which brings the state of the science in HIV prevention directly to people who use drugs in SAN francisco. People who use drugs and are at the highest risk of HIV will be reached via respondent-driven sampling (n=150), leveraging an existing cohort study and connections to social networks of people who use drugs in SAN francisco (aim 1). Participants will then be randomized to standard of care clinic linkages or the street prep intervention, which includes access to a mobile health clinic, tailored navigation to address HIV prevention and substance use needs, and transportation to low-barrier drop-in clinics for ongoing healthcare (aim 2). Using a type 2 hybrid effectiveness-implementation randomized trial, we will measure the impact of the street prep intervention on prep uptake and persistence among people who use drugs in SAN francisco. In aim 3, we will assess barriers and facilitators to implementation and evaluate implementation outcomes throughout the course of the study via qualitative interviews with people who use drugs (n=12-15) and staff (n=5-7). We have assembled a highly experienced, multidisciplinary team of investigators, comprised of leading prep, substance use, HIV, and implementation science researchers, addiction medicine and HIV providers, and an experienced biostatistician. If we find the intervention to be effective, we will develop an implementation toolkit to facilitate dissemination of the street prep intervention to other jurisdictions that can use this model to improve prep uptake and persistence among people at risk of HIV who use drugs.