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Drug overdose remains a leading cause of death in the US, with growing rates attributable to illicit fentanyl use. Recent HIV outbreaks among people who inject drugs (PWID) and service disruptions from COVID-19 have renewed concerns on HIV resurgence. We examined the relationship between fentanyl use and three injection-related HIV risk behaviors among PWID in Baltimore City (BC) and Anne Arundel Country (AAC), Maryland. PWID (N = 283) were recruited to the study through targeted sampling at street-based locations in BC and AAC from July 2018 to March 2020. Receptive syringe sharing (RSS) [adjusted odds ratio (AOR): 2.8, 95% confidence interval (CI): 1.2-6.3] and daily injecting (AOR: 1.9, 95% CI: 1.0-3.6) were associated with injecting fentanyl and cocaine together. Fentanyl availability and COVID-19 bring new HIV prevention challenges, particularly among those who inject fentanyl with cocaine, highlighting the importance to expand and sustain harm reduction, prevention, and treatment services for PWID to reduce HIV and overdose burden., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

HIV remains elevated among female sex workers (FSW) globally, with a number of structural (e.g., poverty, access to care) factors driving these persistently high rates. Pre-exposure prophylaxis (PrEP), a user-controlled prevention method, is a promising means of empowering vulnerable populations to protect themselves and enhance agency. Yet there is a dearth of PrEP research and interventions targeting cisgender women in the United States, and even fewer aimed to reach FSW. We developed and implemented a multifaceted PrEP pilot intervention, the Promoting Empowerment And Risk Reduction (PEARL) study, to meet this gap. This paper describes the development process and nature of a community-informed intervention for tenofovir/emticitrabine (TDF/FTC) pre-exposure prophylaxis engagement among street-based cisgender FSW in Baltimore, Maryland, U.S. In the course of the study's implementation, structural, programmatic, and medical barriers have already posed significant barriers to full engagement. PEARL implemented a number of strategies in an effort to counter barriers and facilitate increased success of PrEP uptake and maintenance. The study will provide critical insights into the nature of intervention components that could help FSW to initiate PrEP and reduce PrEP care cascade gaps.