"It's Not Just One Decision, It's a Whole Lifestyle Change": Mixed Methods Analysis of Factors Associated with Readiness to Change Substance Use Patterns Among Community Recruited People Who Inject Drugs.

: Understanding socio-cultural factors associated with motivation to seek treatment is critical to addressing persistent mortality related to injection and opioid drug use. : Using mixed methods, we examined factors associated with readiness to change substance use among structurally vulnerable people who inject drugs (PWID), recruited from Los Angeles and Denver ( = 472) between 2021 and 2022. : Readiness was categorized into three stages: pre-contemplation (190/386; 49%), contemplation (120/386; 31%), and preparation (76/386; 20%) to quit drug use within six months, three months, or immediately, respectively. Pre-contemplation served as the referent category ( = 386) in multinomial logistic regression analyses controlling for confounding. We found contemplation stage was significantly associated with daily speedball use (mixture of opioid with cocaine) (Adjusted odds ratio [AOR] =4.88; 95% confidence interval [CI] = 1.65, 14.29) and infective endocarditis symptoms (AOR = 3.13;95% CI = 1.54, 6.58). Preparation was associated with infective endocarditis symptoms (AOR = 2.92; 95% CI = 1.28, 6.66) and receiving general relief (AOR = 2.27; 95% CI = 1.28, 4.00). Thematic analysis of semi-structured qualitative interviews with a sample of 30 PWID in Los Angeles revealed barriers to change, including lack of social support and difficulties in altering substance-use routines. Many PWID expressed interest in changing opioid use after significant life events (e.g., incarceration or non-fatal opioid overdose). : Findings suggest that major life events, infectious disease symptoms, and engagement with support programs contribute to increased readiness for substance use disorder treatment.