Abstract
The opioid epidemic has led to an infectious diseases syndemic, with injection drug use responsible for driving rising rates of HIV, viral hepatitis, and serious bacterial and fungal infections. Opioid use continues to cause devastating mortality, with over 80,000 opioid-involved overdose deaths in the USA in 2022. Despite the proven effectiveness of opioid agonist therapy, specifically methadone and buprenorphine, treatment coverage remains inadequate, with profound gaps in opioid use disorder (OUD) continuum of care. Injection-related infections, particularly skin and soft tissue infections, bacteremia, osteomyelitis, and infective endocarditis, have increased substantially since the early 2000s and carry a high risk of morbidity and mortality. Risk is further compounded by criminalization, stigma, incarceration, and comorbid psychiatric conditions. Emerging concerns such as xylazine-associated necrotic wounds illustrate the dynamic intersection of substance use and infectious disease. While direct-acting antivirals have made hepatitis C curable, barriers to treatment persist, and uptake of HIV prevention strategies, including pre-exposure prophylaxis, remains low among people who inject drugs. Integration of addiction treatment into infectious disease and hospital care improves outcomes, yet systemic and policy barriers limit access. Innovative models such as syringe service programs, mobile units, and inpatient addiction consult services demonstrate the feasibility of integrated, patient-centered care. Evidence gaps remain regarding optimal antibiotic strategies for serious infections in people with OUD, and research and policy must address exclusionary practices, stigma, and fragmented systems of care. A synergistic approach integrating OUD treatment, infectious disease management, risk reduction, and trauma-informed care is essential to reduce preventable deaths and improve long-term health outcomes.