Background:
Lipidomics, the analysis of the composition and concentrations of lipid classes and species, may provide greater mechanistic insight into the basis of cardiovascular disease (CVD). This study examined the changes in the lipidome and associations with immune activation in youth living with perinatally acquired HIV (PHIV).
Methods:
The serum lipidome, including 850 different lipid species across 13 lipid classes, as well as the fatty acid composition of these molecules, was measured by direct infusion-tandem mass spectrometry from 100 ART-treated PHIV and 98 age- and sex-matched HIV- Ugandan children at baseline and 96 weeks. All participants were between 10-18 yrs of age. PHIVs had HIV-1 RNA level ≤50 c/mL. In addition, plasma markers of systemic inflammation (hsCRP, IL6), monocyte activation (sCD14 and sCD163), gut integrity and translocation (I-FABP and BDG) were measured by ELISA. T cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+ T cells) was measured by flow cytometry. Comparisons of lipid concentrations between groups were evaluated using 2-sample t-test. Spearman correlations were used to assess correlations between changes in lipid concentration and immune activation.
Results:
Overall, median age [IQR] was 12 years [11-14]; 52% were females. In PHIV, median CD4+ cell counts were 988 cells/µL, and 85% had viral load <50 copies/mL throughout the study. Total cholesterol, LDL, and HDL were similar between the groups, however, the concentrations of ceramides, diacylglycerols, free fatty acids, lysophysophatidylcholines and phosphatidylcholines, were significantly higher in PHIV (P≤0.03). A network figure highlights the associations between changes in lipid species concentrations and inflammatory biomarkers over 96 weeks with a correlation >|0.4|. Notable trends included the predominant association with increases in unsaturated triacylglycerols with increase in activated CD4+ and CD8+ T cells and in fungal translocation, and with decreases in sCD14 and IFAB.
Conclusions:
Despite similar basic lipid panels as HIV-, virologically suppressed PHIV on ART have elevated lipid species that are known to be associated with CVD. Our network analysis identified that triacylglycerols with long and unsaturated acyl chains, previously shown to be associated with an increased risk of plaques in adults living with HIV, are associated with immune activation and fungal translocation. Further studies are warranted to determine whether these lipid species may serve as novel biomarkers.
