Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8-18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.