Long-term, bidirectional associations between depressive symptom severity and opioid use among people with HIV: A prospective cohort study.

Publication date: Dec 01, 2025

The bidirectional relationships between opioid use and depressive symptom severity among people living with HIV (PLHIV) are poorly understood. We hypothesized that higher opioid use frequency would be associated with greater subsequent depressive symptom severity and that greater depressive symptom severity would be associated with higher subsequent opioid use frequency. We analyzed data from the Veterans Aging Cohort Study (VACS) – survey sample, a prospective cohort including PLHIV receiving care at 8 US Veterans Health Administration sites. From 2002 to 2018, we assessed past year opioid use frequency based on self-reported heroin and/or prescription opioid use at study entry and follow-up, as well as depressive symptom severity. Time-lagged, generalized estimating equation models were used to construct estimates of the association between opioid use frequency and subsequent depressive symptom severity, and vice versa, adjusting for key sociodemographic and clinical characteristics. In final adjusted models that included 2033 PLHIV (98 % male), subsequent depressive symptom severity was greater (adjusted odds ratio [aOR] = 1. 44, 95 % CI: 1. 22,1. 70) for those who used opioids at least monthly compared to those who never used, and the association between these variables appeared to follow a dose-response pattern. Similarly, subsequent opioid use frequency was higher (aOR = 1. 38, 95 % CI: 1. 17,1. 62) for those with moderate depressive symptom severity compared to those with none. Enhanced access to screening for substance use disorders, harm reduction services, and medications for opioid use disorder may be warranted in settings that serve veteran PLHIV; strategies expanding access to mental health services may also be promising.

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