Paper # 862 
Association of Vascular Biomarkers with Neurodevelopmental Outcomes in Children with Perinatally Acquired HIV Infection
Suad Kapetanovic*1, E Leister2, S Nichols3, T Miller4, K Tassiopoulos2, R Hazra5, A Mendez4, P Brouwers5, K Malee6, P Williams2, and the Pediatric HIV/AIDS Cohort Study Team
1Univ of Southern California, Keck Sch of Med, Los Angeles, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Univ of California, San Diego, US; 4Univ of Miami Miller Sch of Med, FL, US; 5NIH, Bethesda, MD, US; and 6Northwestern Univ, Feinberg Sch of Med, Chicago, IL, US
Background: Vascular dysfunction has been associated
with Central Nervous System (CNS) disease in adults infected with HIV, but its
role in pediatric HIV is unclear. Better understanding of this role is needed
for development of neuroprotective treatments.
Methods: Neurodevelopmental status was evaluated in
relation to nine selected vascular biomarkers (“biomarkers”) in 89 children
with perinatally-acquired HIV infection enrolled in the Adolescent Master
Protocol (AMP), a prospective cohort study conducted at 15 US sites. Serum levels of the following biomarkers were assessed: P-selectin, fibrinogen,
adiponectin, vascular cell adhesion molecule, monocyte chemoattractant protein,
interleukin-6, C-reactive protein, E-Selectin and intracellular adhesion molecule.
Children enrolled in AMP were administered the Wechsler Intelligence Scale for
Children-IV (WISC-IV) at entry, yielding index scores for Verbal Comprehension,
Perceptual Reasoning, Working Memory and Processing Speed, as well as an
overall composite score (FSIQ). Linear regression models were used to evaluate
the neurodevelopmental outcomes (measured with WISC-IV) as a function of each
biomarker while adjusting for demographics, disease severity and receipt of Highly
Active Antiretroviral Therapy (HAART). Biomarker levels were evaluated as high
versus low, as continuous outcomes, and in quartiles to evaluate dose-response
trends.
Results: In this study, 89 children in AMP
had vascular biomarkers and neurodevelopmental outcomes measured, median age = 12
years, 56% female, 71% Black, 16% Hispanic. Log (P-selectin) was significantly
associated with all 4 index scores and FSIQ, with adjusted slopes indicating a
7 to 11 point average decrease in scores for each one log unit increase in
P-selectin. Final adjusted linear regression models for log (fibrinogen) also
indicated a negative association with all scores, with estimated decreases of
about 13 to 30 points for each one log unit increase in fibrinogen. These
decreases were significant in the Verbal Comprehension, Perceptual Reasoning,
and FSIQ scores. All associations of the WISC-IV scores with these 2 biomarkers
persisted after adjustment for significant sociodemographic and HIV disease
characteristics.
Conclusions: These findings suggest a significant role
of procoagulant and/or inflammatory mechanisms in the pathophysiology of CNS
disease in children and adolescents with perinatally acquired HIV infection.
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