BACKGROUND: This study examined the changes in the lipidome and associations with immune activation and cardiovascular disease (CVD) markers in youth with perinatally acquired human immunodeficiency virus (YPHIV). METHODS: The serum lipidome was measured in antiretroviral therapy (ART)-treated YPHIV (n = 100) and human immunodeficiency virus-uninfected children (n = 98) in Uganda. Plasma markers of systemic inflammation, monocyte activation, gut integrity, and T-cell activation, as well as common carotid artery intima media thickness and pulse wave velocity (PWV), were evaluated at baseline and 96 weeks. RESULTS: Overall, median age was 12 years, and 52% were females. Total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein were similar between the groups
however, the concentrations of ceramides, diacylglycerols, free fatty acids, lysophosphatidylcholines, and phosphatidylcholines were higher in YPHIV (P ≤ .03). Increases in phosphatidylethanolamine (16:0 and 18:0) correlated with increases in soluble CD163, oxidized LDL, C-reactive protein, intestinal fatty acid binding protein, and PWV in YPHIV (r ≥ 0.3). CONCLUSIONS: YPHIV successfully suppressed on ART have elevated lipid species that are associated with CVD, specifically palmitic acid (C16:0) and stearic acid (C18:0).