Background:
Data suggest that adverse childhood experiences (ACEs) are associated with an increased risk of cardiovascular disease (CVD). However, little data exist on the effect of ACEs and health in children. We examined the relationship between ACEs and CVD risk factors in youth living with perinatally acquired HIV (YPHIV) in Uganda.
Methods:
A prospective observational cohort study was performed in 49 YPHIV and 51 HIV- from 2017-2021 at the JCRC in Uganda at baseline and 96 weeks later. All participants were between 10-18 years of age. YPHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. Mean common carotid artery intima-media thickness (IMT), pulse wave velocity (PWV), plasma and cellular markers of systemic inflammation and immune activation were evaluated at baseline and 96 weeks. The Adverse Childhood Experiences-International Questionnaire (ACEs), Patient Health Questionnaire-9 (PHQ-9) and socioeconomic questionnaires were administered, and ACEs sub scored of abuse, neglect and household dysfunction (HHDYS) were calculated. Hierarchical cluster analysis was performed to identify natural clusters of ACEs and socioeconomics.
Results:
At baseline, median age was 12 years (IQR: 11-14), 52% were female. YPHIV were more likely to have a history of abuse, and higher ACE total scores (p=0.015). Two optimal clusters were derived from ACEs, PHQ-9 mean scores, and socioeconomic variables (figure 1). Compared to cluster 1, participants in cluster 2 had higher ACEs (p≤0.001 for all), and were more likely to have: HIV (69% vs 42%, p=0.019), higher levels of monocytes and T cell activation (CD14+CD6- and CD14+CD16+% monocytes; CD8 expressing CD38 and HLA DR, p≤0.037); higher systolic blood pressure (p=0.040), and higher increases in PWV over 96 weeks (p=0.047). In mixed linear regression models adjusting for HIV status, age, gender, physical activity (met-kcal/hour), mean PHQ-9 score, monocytes, activated CD8 T cells, total ACE score (β=0.10) and HHDYS (β=-0.09) remained associated with a higher change in PWV over 96 weeks.
Conclusions:
Findings suggest that ACEs may contribute to CVD risk in YPHIV in Uganda, even after adjusting for factors known to influence cardiovascular health. Early life stress may play an important role on inflammation and cardiovascular health in this setting. Further research is warranted to determine the impact of emotional events on physical outcomes in HIV, whether this is a potentially modifiable risk factor, and how to mitigate long-term consequences.
