Association of childhood adversity and depression with cardiovascular health in youth with perinatal HIV 1 in Uganda

While adverse childhood experiences (ACEs) are known to increase cardiovascular disease (CVD) risk, their effects among youth living with perinatally acquired HIV (YPHIV) are not well characterized. In this study, we investigated associations between ACE exposure and early CVD risk among Ugandan YPHIV and youth without perinatally acquired HIV (YWoH). In a 96-week prospective cohort, 49 YPHIV and 51 YWoH (ages 10–18) were enrolled at the Joint Clinical Research Center, Uganda. YPHIV were on antiretroviral therapy with HIV-1 RNA ≤ 400 copies/mL. The primary outcome, pulse wave velocity (PWV), defined as the 96-week-to-baseline ratio, and secondary outcomes including carotid intima-media thickness (IMT), BMI, inflammatory biomarkers, and depressive symptoms (PHQ-9) were assessed at baseline and week 96. Participants completed the ACE–International Questionnaire, PHQ-9, and socioeconomic surveys. ACE sub-scores (abuse, neglect, household dysfunction) were derived. Hierarchical clustering , performed using R, identified ACE–socioeconomic exposure patterns . Regression models with an interaction term of HIV status and ACE category or total ACE score were used to evaluate whether the association between ACE and outcomes differed by HIV status using SAS Enterprise Guide. Median age was 13 years (IQR 12–14); 48% were female. YPHIV had higher total ACE scores than YWoH ( p = 0.003). Two exposure clusters were identified; cluster 2 demonstrated higher ACE exposure ( p ≤ 0.001 across subdomains), a greater proportion of YPHIV ( p = 0.019), increased monocyte and T-cell activation ( p ≤ 0.037), higher systolic blood pressure ( p = 0.040), and greater PWV progression ( p = 0.047). In regression models, after adjustment for demographic, behavioral, and inflammatory factors, only neglect showed a significant interaction with HIV status, indicating greater PWV progression among YPHIV (β = 0.292, SE = 0.139, p = 0.041). ACEs, particularly neglect, were independently associated with arterial stiffness in Ugandan YPHIV. Early life stress may influence inflammation and CVD risk, highlighting the need for early interventions to mitigate long-term consequences.