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Introduction: People who inject drugs (PWID) are disproportionately affected by HIV in the United States, and HIV prevention and care services may be inaccessible to or underutilized by PWID. In 2018, the Massachusetts Department of Public Health (MDPH) and the Centers for Disease Control and Prevention (CDC) investigated an increase in HIV diagnoses primarily among unstably housed PWID in Lawrence and Lowell., Methods: The response team interviewed 34 PWID in Lawrence and Lowell, with and without HIV, to inform effective response strategies. Qualitative interviews were recorded, transcribed, and coded. Interviews were transcribed verbatim and coded using a thematic analysis approach structured around pre-designated research questions related to service engagement (including harm reduction services, substance use disorder treatment, medical services, shelters, and other community services), unmet needs, and knowledge gaps regarding HIV prevention., Results: Participants ranged in age from 20 to 54 years (median: 32); 21 of the 34 participants (62%) were male, and 21 were non-Hispanic white. Fifteen (44%) self-reported being HIV positive. All 34 participants had experienced homelessness in the past 12 months, and 29 (85%) had ever received services at syringe service programs (SSP). We identified five key themes: substance use as a barrier to accessing health and social services; experiences of trauma and mental illness as factors impacting substance use and utilization of services; unstable housing as a barrier to accessing services; negative perceptions of medication for opioid use disorder (MOUD); and the desire to be treated with dignity and respect by others., Conclusions: Findings highlight the need for well-resourced and integrated or linked service provision for PWID, which includes mental health services, housing, MOUD, harm reduction, and infectious disease prevention and care services. Co-locating and integrating low-barrier services at trusted community locations, such as SSPs, could increase service engagement and improve health outcomes for PWID. Further implementation science research may aid the development of effective strategies for services for PWID and build trusting relationships between service providers and PWID., (Published by Elsevier Inc.)