Abstract
BACKGROUND: Depression is a common psychiatric condition and an independent stroke risk factor among people with HIV (PWH). The impacts of depressive symptom severity on stroke are not clear in PWH. METHODS: We studied adult PWH in clinical care at 5 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites with ≥1 assessment for depressive symptoms (Patient Health Questionnaire-9) from 2010 to 2022. We used Cox models to evaluate (1) associations between time-varying depressive symptom severity and adjudicated incident stroke, serially adjusted for clinical factors and (2) modification of this association by age and sex. Participants were followed from 6 months after first CNICS visit or date the CNICS site began stroke adjudication (baseline) (whichever later) until the first stroke, death, loss to follow-up, last clinic visit, or study end. RESULTS: Among 13,817 PWH (mean age 45 years, 19% women, 58% non-White race/ethnicity), 23% screened positive for depression at baseline and 173 had an incident stroke during follow-up (mean follow-up 7.6 years). Time-varying depressive symptom severity (per 5 points Patient Health Questionnaire-9 score) was associated with higher stroke risk (adjusted Hazard Ratio 1.16, P = 0.01) with greater impact in PWH <50 years than ≥50 years (interaction P = 0.02) but no significant difference by sex. Adjusting for combinations of sociodemographic, cardiovascular, HIV, and substance use factors only slightly attenuated estimates. CONCLUSIONS: Depressive symptom severity was an independent risk factor for stroke with higher severity depressive symptoms predicting higher stroke risk and greater impact in PWH <50 years. Depression may be a modifiable risk factor for stroke and should be studied further to understand, develop, and target interventions to reduce stroke risk, especially in younger PWH.