Lipidome association with vascular disease and inflammation in HIV+ Ugandan children

Abstract

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.

Figure 1:

Median concentrations of lipids CE: cholesterol esters; CER: Ceramides; FFA: Free Fatty Acids; LCER: Lactosylceramides; PC: Phosphatidylcholines; SM: sphingomyelins- Dot plots showing the median lipid levels in children with perinatally acquired HIV (PHIV) and HIV negative children (HIV-). Horizontal lines denote the interquartile range.

Figure 2:

Heat map correlations between lipids (photosphotidylcholine and sphingomyelin) and inflammatory markers in PHIV and HIV- A) Heat map showing the correlation between phosphatidylcholine in children living with perinatally acquired HIV (PHIV) and B) HIV negative children and c) sphingomyelins in PHIV and D) HIV negative children hsCRP: high sensitivity C reactive protein (ng/mL), IL-6: interleukin 6 (pg/mL), sCD14 and 163: soluble CD14 and soluble CD163 (pg/mL), sTNFR-I: soluble tumor nectrosis factor α I (pg/mL), CD4 and CD8 T cells and CD4CD38: CD4+HLA-DR+ T cells, CD8CD38:CD8+HLA-DR+ T cells; PC: phosphatidylcholine; SM: sphingomyelin *for p <0.05;

Figure 3:

Correlation of Free Fatty Acids with IMT among PHIV and HIV- participants A) Correlation of FFA with IMT in PHIV, B) Correlation of FFA with IMT in HIV- FFA: Free Fatty Acids, IMT: intima media thickness, PUFA: polyunsaturated fatty acids, MUFA: monounsaturated fatty acids, SaFA: saturated fatty acids *= p value ≤0.05, ** for p<0.01