Impact of Depressive Symptom Severity on Stroke Risk in a US Cohort of People with HIV

Jimmy Ma; Robin M Nance; Stephanie A Ruderman; Lydia N Drumright; L Sarah Mixson; Felicia C Chow; Joseph Zunt; Christina M Marra; Maile Karris; Emily L Ho; Kyra Becker; Rizwan Kalani; Andrew Huffer; Rob Fredericksen; Sonia Napravnik; Richard D Moore; Barbara Gripshover; Amanda Willig; Jacklyn D Foley; Greer Burkholder; Michael S Saag; Katerina Christopoulos; Mari M Kitahata; David Tirschwell; Joseph A C Delaney; Heidi M Crane

doi:10.1097/QAI.0000000000003710

Impact of Depressive Symptom Severity on Stroke Risk in a US Cohort of People with HIV

J Acquir Immune Defic Syndr. 2025 Jun 20. doi: 10.1097/QAI.0000000000003710. Online ahead of print.

Authors

Jimmy Ma¹, Robin M Nance¹, Stephanie A Ruderman¹, Lydia N Drumright², L Sarah Mixson¹, Felicia C Chow³, Joseph Zunt⁴, Christina M Marra⁴, Maile Karris⁵, Emily L Ho^{4

6}, Kyra Becker⁴, Rizwan Kalani⁴, Andrew Huffer⁴, Rob Fredericksen¹, Sonia Napravnik⁷, Richard D Moore⁸, Barbara Gripshover⁹, Amanda Willig¹⁰, Jacklyn D Foley¹¹, Greer Burkholder¹⁰, Michael S Saag¹⁰, Katerina Christopoulos¹², Mari M Kitahata¹, David Tirschwell⁴, Joseph A C Delaney^{1

13}, Heidi M Crane¹

Affiliations

¹ Department of Medicine, School of Medicine, University of Washington, Seattle, WA.
² Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, WA.
³ Weill Institute for Neurosciences, Departments of Neurology and Medicine (Infectious Diseases), School of Medicine, University of California San Francisco, San Francisco, CA.
⁴ Department of Neurology, School of Medicine, University of Washington, Seattle, WA.
⁵ Department of Medicine, School of Medicine, University of California San Diego, San Diego, CA.
⁶ Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA.
⁷ Department of Epidemiology, School of Public Health, University of North Carolina Chapel Hill, Chapel Hill, NC.
⁸ Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD.
⁹ Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH.
¹⁰ Department of Medicine, School of Medicine, University of Alabama-Birmingham, Birmingham, AL.
¹¹ Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
¹² Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, CA.
¹³ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.

PMID: 40539652
DOI: 10.1097/QAI.0000000000003710

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 five CNICS sites with ≥1 assessment for depressive symptoms (PHQ-9) from 2010-2022. We used Cox models to evaluate: (1) associations between time-varying depressive symptom severity and adjudicated incident stroke, serially adjusted for clinical factors; (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% female, 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 PHQ-9 score) was associated with higher stroke risk (aHR 1.16, P=0.01) with greater impact in PWH <50y than ≥50y (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.

Keywords: (5-7 words): depression; HIV; depressive symptom severity; stroke.