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.
Kapetanovic
Suad
S
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
Leister
Erin
E
Nichols
Sharon
S
Miller
Tracie
T
Tassiopoulos
Katherine
K
Hazra
Rohan
R
Gelbard
Harris A
HA
Malee
Kathleen M
KM
Kammerer
Betsy
B
Mendez
Armando J
AJ
Williams
Paige L
PL
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