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Published on: January 12, 2016
Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected
Suad Kapetanovic1, Erin Leister, Sharon Nichols
1Maternal, 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
Insights
Vascular dysfunction markers, specifically soluble P-selectin and fibrinogen, are linked to lower neurodevelopmental scores in children with HIV. These findings suggest inflammation may impact cognitive function in pediatric HIV disease.
Area of Science:
- Pediatric HIV research
- Neurodevelopmental disorders
- Vascular biology
Background:
- Pediatric HIV infection can lead to long-term health complications.
- Neurodevelopmental impairments are a concern in children living with HIV.
- Vascular dysfunction is increasingly recognized as a factor in chronic diseases.
Purpose of the Study:
- To investigate the association between vascular dysfunction markers and neurodevelopmental status in children with HIV.
- To identify specific biomarkers that correlate with cognitive deficits in pediatric HIV.
Main Methods:
- Cross-sectional analysis of 89 HIV-infected children from a prospective US cohort.
- Measured nine vascular biomarkers (e.g., soluble P-selectin, fibrinogen) and cognitive function using the Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV).
- Employed linear regression models, adjusting for covariates, to assess biomarker impact on WISC-IV scores.
Main Results:
- Elevated levels of soluble P-selectin and fibrinogen were significantly correlated with lower WISC-IV scores across multiple domains.
- Each log unit increase in soluble P-selectin correlated with a 6-11 point decrease in WISC-IV scores.
- Each log unit increase in fibrinogen correlated with a 13-30 point decrease in Full-Scale IQ and other cognitive measures.
Conclusions:
- Proinflammatory microvascular and immunologic pathways may contribute to neurodevelopmental impairment in children with perinatally acquired HIV.
- Specific vascular biomarkers like soluble P-selectin and fibrinogen show a detrimental relationship with cognitive function.
- Further research into these mechanisms could inform interventions for cognitive deficits in pediatric HIV.
Objective:
To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease.
Design:
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.
Conclusion:
Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease.
