Introduction Prescription drug abuse is a major public health problem in rural and suburban areas of the United States, however its emergence in large urban settings with endemic injection drug use remains understudied. We examined temporal trends in injection drug use initiation and mortality among people who inject drugs (PWID) in Baltimore, Maryland. Methods Data were derived from the baseline assessment of PWID enrolled in a community-based cohort study with longitudinal follow-up for mortality assessment. PWID were recruited from 2005–2008 (N = 1,008) and 2015–2018 (N = 737). We compared characteristics by birth cohort (before/after 1980) and type of drug initiated (prescription opioids, prescription non-opioids, non-injection illicit drugs, or injection drugs). We calculated standardized mortality ratios (SMR) using the US general population as the reference. Results PWID born after 1980 were more likely to initiate drug use with prescription opioids and non-opioids and had higher levels of polysubstance prior to injection initiation, compared to individuals born before 1980. Overall mortality was high: 2.59 per 100 person-years (95% CI: 2.27–2.95 per 100 person-years). Compared to the US population, the highest SMRs were observed among participants between 40–44 years of age, with especially high mortality among women in this age group (SMR:29.89, 95% CI: 15.24–44.54). Conclusions Mirroring national trends, the profile of PWID in Baltimore has changed with increased prescription drug abuse and high levels of polysubstance use among younger PWID. Interventions need to reach those using prescription drugs early after initiation of use in order to reduce transition to injecting. Urgent attention is warranted to address premature mortality, particularly among middle-aged and female PWID.
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