Abstract
BACKGROUND: Polysubstance use (PSU) is common among people who use opioids (PWUO) and has been associated with drug-related harms. We aimed to identify latent longitudinal PSU classes among a cohort of PWUO and characterize non-fatal overdose risks among different sub-classes over time. METHODS: We used longitudinal data (2005-2018) from three ongoing prospective cohorts of people who use drugs in Vancouver, Canada. The primary outcome of interest was self-reported non-fatal overdose during the past six months. The primary exposure of interest was longitudinal PSU patterns among PWUO, obtained from repeated measures latent class analysis (RMLCA) of weekly substance use-related outcome indicators. Multivariable generalized estimating equations models were built to assess the association between latent PSU class membership and non-fatal overdose, adjusting for potential sociodemographic, behavioural, and structural confounders. RESULTS: 2627 PWUO were included in the analysis, and 1094 (41.6 %) had experienced at least one non-fatal overdose during the study period. RMLCA revealed five distinct latent longitudinal PSU classes, including low/infrequent use (Class 1; 30 %), primarily opioid and methamphetamine use (Class 2; 22 %), primarily cannabis use (Class 3; 15 %), primarily opioid and crack use (Class 4; 29 %), and frequent PSU (Class 5; 4 %). In comparison with Class 1 (low), membership in all latent PSU classes except Class 3 (cannabis) was associated with increased odds of non-fatal overdose: Class 2 (opioids + meth) vs. Class 1 (Adjusted odds ratios [aOR] = 2.20, 95 % confidence intervals [CI]: 1.51-3.22), Class 4 (opioids + crack) vs. Class 1 (aOR = 1.06, 95 % CI: 0.85-1.33), and Class 5 (frequent) vs. Class 1 (aOR = 2.39, 95 % CI: 1.92-2.97). CONCLUSION: Our findings highlighted the heterogeneous characteristics of PWUO in terms of patterns of PSU and non-fatal overdose risk. The diverse nature of PWUO and the potential additive or multiplicative impact of using several substances on overdoses should be reflected across the substance use treatment continuum and care provision.