Despite effective virological suppression with cART, children perinatally infected with HIV show neuropsychological dysfunctioning with underlying macro- and microstructural brain injury. The potential role of vascular comorbidity and cerebral blood flow (CBF) in these deficits is unclear. This study aimed to assess whether CBF and vascular disease biomarkers were associated with cerebral and cognitive deficits in HIV-infected children.
This cross-sectional study included 36 cART-treated perinatally infected children aged 8-18 years from the Academic Medical Center in Amsterdam, and 37 age-, sex-, ethnicity- and socio-economic status-matched uninfected controls. We measured markers of inflammation, endothelial activation (using MesoScale Discovery), and coagulation (using enzyme-linked immunosorbent assays) in blood samples from all participants and in cerebrospinal fluid (CSF) from HIV-infected participants. Using 3-Tesla MRI, we determined CBF (using arterial spin labeling), gray matter (GM) volume, white matter (WM) lesion volume, and WM diffusivity (using diffusion tensor imaging). We explored whether CBF and vascular health markers were associated with MRI abnormalities, and cognitive performance (among others intelligence, processing speed, and visuomotor integration) in HIV-infected children using linear and ordered logistic regression analyses.
HIV-infected children showed higher CBF in WM, caudate nucleus, putamen, nucleus accumbens and thalamus, as well as higher blood levels of CRP and sVCAM-1. Blood and CSF levels of CRP, sVCAM-1, and sICAM-1 were strongly correlated (Table 1). Higher levels of CRP were associated with higher WM mean diffusivity (blood: coef=2.09; P=.029; CSF: coef=2.27; P=.029), and lower GM CBF was associated with higher WM lesion volume (coef=-0.053; P=.001). Vascular markers were not associated with GM volume, WM lesion volume, or CBF. Among cognitive outcomes, only higher blood sVCAM-1 was strongly associated with poorer visuomotor integration (coef=-17.6; P=<.001).
In HIV-infected children, lower GM CBF, and increased inflammation and endothelial activation were associated with WM injury and visuomotor integration. Vascular disease may thus play a role in pediatric HIV-associated cerebral and cognitive deficits. Longitudinal evaluation is warranted to assess whether CBF changes, inflammation and endothelial activation negatively affect white matter health and cognitive performance in this population over time.