BackgroundHIV outbreaks among people who inject drugs (PWID) and experience homelessness are increasing across the USA. Despite high levels of need, multilevel barriers to accessing antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention persist for this population. The Boston Health Care for the Homeless Program (BHCHP) initiated a low-threshold, outreach-based program to support engagement in PrEP services among PWID experiencing homelessness.MethodsTo inform dissemination efforts, we explored patient and provider perspectives on key program components. From March to December 2020, we conducted semi-structured qualitative interviews with current and former BHCHP PrEP program participants and prescribers, patient navigators, and outreach workers (i.e., providers). Thematic analysis explored perspectives on key program components.ResultsParticipants (n = 21) and providers (n = 11) identified the following five key components of BHCHP's PrEP program that they perceived to be particularly helpful for supporting patient engagement in PrEP services: (1) community-driven PrEP education; (2) low-threshold, accessible programming including same-day PrEP prescribing; (3) tailored prescribing supports (e.g., on-site pharmacy, short-term prescriptions, medication storage); (4) intensive outreach and navigation; and (5) trusting, respectful patient-provider relationships.DiscussionFindings suggest that more patient-centered services formed the basis of BHCHP's innovative, successful PrEP program. While contextual challenges including competing public health emergencies and homeless encampment "sweeps" necessitate ongoing programmatic adaptations, lessons from BHCHP's PrEP program can inform PrEP delivery in a range of community-based settings serving this population, including syringe service programs and shelters.