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Published on: October 12, 2017
Lipidome association with vascular disease and inflammation in HIV+ Ugandan children
Sahera Dirajlal-Fargo1,2,3, Abdus Sattar3, Jiao Yu3
1University Hospitals Cleveland Medical Center.
Insights
Children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) show altered lipid profiles. Inflammation is linked to lipid changes and increased cardiovascular disease risk factors in these young patients.
Area of Science:
- Cardiovascular Science
- Immunology
- Pediatric Infectious Diseases
Background:
- HIV infection and antiretroviral therapy (ART) are associated with dyslipidemia and increased cardiovascular disease (CVD) risk.
- The interplay between lipidome, immune activation, and subclinical vascular disease in perinatally acquired HIV (PHIV) remains understudied in children.
Purpose of the Study:
- To investigate the relationships among lipidome, immune activation, and subclinical vascular disease in children with perinatally acquired HIV (PHIV) on ART.
Main Methods:
- Serum lipidomics (13 classes, 850 species) analyzed via mass spectrometry in 20 ART-treated PHIV and 20 HIV-negative children (10-18 years).
- Assessed common carotid artery intima-media thickness (IMT), systemic inflammation markers (hsCRP, IL6, sTNFRa I), monocyte activation (sCD14, sCD163), and T-cell activation (CD38, HLA-DR).
Main Results:
- PHIV children exhibited significantly increased concentrations of cholesterol ester, LCER, phosphatidylcholines, and sphingomyelin lipid classes.
- Biomarkers of CVD risk (hsCRP, sCD163, T-cell activation) directly correlated with specific lipid species in PHIV.
- Free fatty acids (palmitic, stearic, arachidic) positively correlated with IMT in PHIV.
Conclusions:
- Young, virally suppressed PHIV children on ART display significant alterations in their serum lipidome.
- A direct association exists between inflammation and lipid species linked to CVD risk in this pediatric population.
Objective:
HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD). The relationships among the lipidome, immune activation, and subclinical vascular disease in children with perinatally acquired HIV (PHIV) have not been investigated.
Methods:
Serum lipid composition, including 13 lipid classes constituting 850 different lipid species were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated PHIV and 20 age-matched and sex-matched HIV- Ugandan children. All participants were between 10 and 18 years of age with no other known active infections. PHIVs had HIV-1 RNA level 50 copies/ml or less. In addition, common carotid artery intima--media thickness (IMT), as well as plasma marker of systemic inflammation (hsCRP, IL6, sTNFRa I), monocyte activation (soluble CD14 and CD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) were evaluated.
Results:
Median age (Q1, Q3) of study participants was 13 years (11, 15), 37% were boys, 75% were on an NNRTI-based ART regimen. The concentrations of cholesterol ester, LCER, phosphatidylcholines, and sphingomyelin lipid classes were significantly increased in serum of PHIV compared with HIV (P≤0.04). Biomarkers associated with CVD risk including hsCRP, sCD163, and T-cell activation were directly correlated with lipid species in PHIV (P ≤ 0.04). Contents of free fatty acids including palmitic (16 : 0), stearic (18 : 0), and arachidic acid (20 : 0) were positively correlated with IMT in PHIV.
Conclusion:
Serum lipidome is altered in young virally suppressed PHIV on ART. A direct association between inflammation and lipid species known to be associated with CVD was observed.
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