SCD14, SICAM-1, AND SVCAM-1 CORRELATE WITH NEUROCOGNITIVE FUNCTION IN YOUTH WITH HIV
HIV infection affects cognitive performance through immune activation and related mechanisms. We hypothesized that in youth with HIV (YWH), biomarkers of macrophage activation and vascular injury are associated with impairment in distinct neurocognitive domains. YWH, ages 20 to 28, enrolled in ATN 071/101 were assessed for biomarkers of macrophage activation and vascular injury using ELISA/multiplex assays. Participants completed standardized neurocognitive tests. Demographically corrected z-scores were combined to form indices of attention, motor functioning, executive functioning, and both verbal and nonverbal memory. We performed a cross sectional analysis of the relationship between blood levels of four key biomarkers (sCD163, sCD14, sICAM-1, and sVCAM-1) and performance in each of these neurocognitive domains. Linear regression models were fit for the log-transformed biomarker value for each combination of biomarker and cognitive domain score. These models were adjusted for demographics, socioeconomic status, substance use, and depression. Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% male, 68% African American]. We found moderate evidence for the following associations: sCD14 was negatively associated with executive function [adjusted estimate -0.69 (95% CI -1.43, 0.05)] and non-verbal memory [-0.99 (-1.89, -0.10)]. Soluble ICAM-1 was negatively associated with verbal memory [-0.31 (-0.64, 0.03)], while sVCAM-1 was positively associated with attention [0.32 (-0.04, 0.69)], executive function [0.68 (0.29, 1.08)], and non-verbal memory [0.56 (0.04, 1.07)]. Soluble CD163 was not significantly associated with any domain. None of the key biomarkers were significantly associated with the motor domain. Biomarkers of macrophage activation and vascular injury were differentially associated with distinct cognitive domains, especially executive function and memory, among YWH. Intriguing positive associations of soluble VCAM-1 with executive function and nonverbal memory may indicate a link between vascular flow and cognitive performance among YWH who are at early stage of disease.
