Objective: To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.
Design: Cross-sectional design within a prospective, 15-site US-based cohort study.
Methods: Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores.
Results: Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs.
Conclusion: Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.
aNational Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
bDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
cDepartment of Neurosciences, University of California San Diego, San Diego, California
dCenter for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York
eUniversity of Miami Miller School of Medicine, Miami, Florida
fEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
gDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
hFeinberg School of Medicine, Northwestern University, Chicago, Illinois
iDepartment of Psychiatry, Boston Children's Hospital, Boston, Massachusetts, USA.
Correspondence to Suad Kapetanovic, MD, NIH, NIMH Office of the Clinical Director, Bldg. 10-CRC, Room 6-5340, 10 Center Drive, Bethesda, MD 20892-1276, USA. Tel: +1 301 827 2435; fax: +1 301 402 2588; e-mail: firstname.lastname@example.org
Received 20 July, 2013
Accepted 10 September, 2013