Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p= 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p= 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p= 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p= 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p&nbsp