Project Summary: We propose a two-year qualitative study that will characterize transitions to low-frequency injecting and injection cessation among people using xylazine-adulterated fentanyl in one of the states (Connecticut) most impacted by this drug supply change. America's drug supply has grown become more volatile since the outset of the COVID-19 pandemic, particularly the proliferation of xylazine-adulterated fentanyl in Northeast and Mid-Atlantic states, and is driving drug-related harms, including increases in non-fatal and fatal overdoses and severe injection-related soft tissue infections. Amidst the emergence of xylazine-adulterated fentanyl, researchers have begun to document reductions in injection drug use and injection cessation among people continuing to use fentanyl. Transitions to low-frequency injecting and injection cessation represent key strategies for reducing the potential for soft tissue infections associated with xylazine-injecting, as well as the transmission of infectious diseases (e.g., hepatitis C, HIV). However, the growing proportion of overdose deaths across the country attributed to non-injection drug use raise significant concerns about overdose awareness and the responsiveness of harm reduction services to the needs of people transitioning to low-frequency injecting and injection cessation. Contextualized understandings of how the proliferation of xylazine-adulterated fentanyl intersects with social, structural, and environmental influences to shape these transitions to low-frequency injecting and infection cessation and their implications for harm reduction services are urgently needed to optimize harm reduction approaches. Building on our extensive experience studying the impacts of drug supply changes, including on drug use behaviors and harm reduction services, we propose the following specific aims: Aim 1: To characterize how exposure to xylazine-adulterated fentanyl intersects with social-structural influences (e.g., homelessness, poverty) to shape transitions to low-frequency injecting (≤10 times per month) and injection cessation (>30 days). Aim 2: To explore perceptions of overdose vulnerability associated with non-injection drug use of xylazine-adulterated fentanyl, and examine their implications for overdose prevention messaging and harm reduction service delivery. Aim 3: To explore challenges and opportunities for harm reduction strategies, including syringe exchange, naloxone, and community health programs, in addressing overdose vulnerability among people exposed to xylazine-adulterated fentanyl transitioning to low-frequency injection drug use or injection cessation. Informed by the equity-focused Intersectional Risk Environment framework, we will conduct qualitative interviews with people using xylazine-adulterated fentanyl across Connecticut (n=50) who have transitioned to low-frequency injecting or injection cessation (Aims 1&2), as well as focus groups with harm reduction workers (n=30) from...