VEGF Is a Stronger Predictor of Depressive Symptoms than Other Inflammation Markers in People with HIV on Antiretroviral Therapy

People with HIV (PWH) experience higher rates of depression compared with the general population. Inflammation has been associated with depressive symptoms and may be associated with a subtype of depression, but the relationship between inflammation and depressive symptoms in PWH on antiretroviral therapy (ART) is unclear. In this study, inflammation biomarkers (IFN-γ, IL-1β, IL-6, IL-8, IL-12p70, IL-15, IP-10, MCP-1, VEGF, CRP) were measured in plasma from 195 PWH on ART and depressive symptoms were assessed using Beck Depression Inventory-II (BDI-II) scores. Logistic regression and mixed-effects models were used to examine the associations between inflammation biomarkers and depressive symptoms at baseline and over 18 months of follow-up. PWH had a median age of 52 years, with 95% being virally suppressed below 200 copies/mL, 33% having high depressive symptoms, and 62% having ≥1 medical comorbidity (HCV, cardiovascular disease, diabetes, chronic kidney disease, chronic lung disease). VEGF levels were increased in PWH with high vs. low depressive symptoms (p = 0.01). The association between VEGF and depressive symptoms remained significant in covariate-adjusted models (p = 0.005) and was augmented in PWH with medical comorbidities (p = 0.002). Other inflammation biomarkers were increased in PWH with medical comorbidities, but not significantly different between groups stratified by depressive symptoms. Among PWH with high depressive symptoms, biomarker clustering identified inflammatory and noninflammatory subgroups distinguished by levels of VEGF/MCP-1/IL-8 or IL-6/CRP and prevalence of HCV, cardiovascular disease, and diabetes. These findings suggest that VEGF is a biomarker associated with depressive symptoms in PWH on ART and may identify a subtype of depression for targeted interventions.