Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth.
OBJECTIVE
To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease.


METHODS
A cross-sectional design within a prospective, 15-site cohort study conducted in the United States.


METHODS
Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, and soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) was administered yielding indices for verbal comprehension, perceptual reasoning, working memory and processing speed, and overall composite Full-Scale IQ score. Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity, and receipt of HAART. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses.


RESULTS
Among the 89 HIV-infected children (median age = 12 years), 56% were girls, 71% black, 16% Hispanic, and 43% had yearly household income below US $20,000. Log (soluble P-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6-11-point average decrease in scores for each one log unit increase in soluble P-selectin. Final linear regression models for log (fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13-30-point decrease for each one log unit increase in fibrinogen); these decreases were significant in the verbal comprehension, perceptual reasoning, and Full-Scale IQ scores.


CONCLUSIONS
Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease.
Maternal, Child and Adolescent Center for Infectious Diseases and Virology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. kapetano@usc.edu
Suad
S
Kapetanovic
Erin
E
Leister
Sharon
S
Nichols
Tracie
T
Miller
Katherine
K
Tassiopoulos
Rohan
R
Hazra
Harris A
HA
Gelbard
Kathleen M
KM
Malee
Betsy
B
Kammerer
Armando J
AJ
Mendez
Paige L
PL
Williams
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000821:virology; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D002648:Child; D003072:Cognition Disorders / Q000097:blood / Q000503:physiopathology* / Q000821:virology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral; D014481:United States; D019562:Viral Load
D015415:Biomarkers; D012367:RNA, Viral