A binational cohort of the intersection between substance use, HIV, and associated comorbidities among people who inject drugs in San Diego, CA - We will prospectively study the intersection between substance use, HIV and related co-morbidities in a cohort of people who use drugs (PWUD) in San Diego County (SD). For >25 years, Strathdee has studied the epidemiology of HIV and related co-infections among PWUD across North America, with N=500-1000 and annual retention ≥90%. Since 2020, our La Frontera I cohort situated on the U.S.-Mexico border has documented the highest HIV and HCV incidence among people who inject drugs in North America. Currently, HIV prevalence among former injectors in SD is 16% compared to 10% among current injectors. Consistent with other U.S. cities, we observed a dramatic shift from injection to non-injection of opiates in recent years, leading us to propose cohort expansion to non-injectors. Due to our location on a major drug trafficking corridor, we observe a wide range of substances (e.g., heroin, fentanyl, methamphetamine, xylazine, benzodiazepines). We previously leveraged La Frontera I to evaluate initiatives to improve uptake of PrEP, COVID-19 testing and vaccination. We propose: 1) To characterize trends and predictors of use of established and emerging drugs, drug use transitions (e.g., shifts from IDU to non-IDU & vice versa) and their impact on HIV incidence and utilization of HIV prevention and treatment. 2) To study prevalence and incidence of the following co-morbidities and their relationship to HIV incidence and utilization of HIV prevention and treatment: i) HCV; ii) STIs (i.e., syphilis, gonorrhea, Chlamydia, MPox), iii) neurobehavioral disturbances. 3) To evaluate the influence of structural interventions on HIV-related risk behaviors and utilization of HIV prevention and treatment including: i) new homelessness policies; ii) drug checking services; iii) vending machines. 4) To contribute to a shared database and biorepositories that serve as a platform for collaborations with end users and community partners. To meet these aims, we will continue to follow PWUD from La Frontera I who are actively using illicit substances, replenishing to arrive at 500 PWID and 500 PWUD (non-injectors) for a total sample of 1000. This will include subgroups vulnerable to HIV in SD (e.g., sex workers, people experiencing homelessness) among whom we expect 52 HIV seroconversions after 5 years of follow-up. Our cohort will include at least 50 PWUD living with HIV who will provide samples for viral load, sequencing and biobanking. All participants will undergo semi-annual interviews and specimen collection. SD is designated as a high priority jurisdiction for the Ending the HIV Epidemic Initiative (EHE) and a high intensity drug trafficking area by the DEA. La Frontera II leverages NIH-funded T32s, the California NeuroHIV Tissue Network, Last Gift Study brain/tissue repositories and the PREPARE Institute which tracks emerging and re-emerging infectious disease threats. Our work is aligned with priorities identified by RFA-DA-25-003, the NIH Office of AIDS Research and the EHE.
