Abstract P186: Plasma Ceramides Are Associated With HIV Treatment and Increased Risk of Carotid Artery Plaque in Two Prospective HIV Cohorts

Abstract

Introduction: Ceramides, a family of bioactive sphingolipids on plasma membrane, have been implicated in inflammation, immune response, and HIV infection. Recent studies have related plasma ceramides with cardiovascular diseases (CVD), but data are sparse in HIV infected people who have excess CVD risk. Methods: We profiled baseline plasma ceramides C16:0, C22:0, C24:0 and C24:1 in 737 participants aged 35-55 years (520 HIV+, 217 HIV-) from two prospective cohorts (Women’s Interagency HIV Study and Multicenter AIDS Cohort Study) and examined their associations with the risk of incident carotid artery plaque (CAP), assessed by B-mode carotid artery ultrasound imaging over a 7-year period. Plasma levels of ceramides were inverse-normal transformed. We used robust variance estimates from Poisson regression to estimate risk ratios (RRs) on CAP per standard deviation increment in ceramides. We also compared ceramide levels by HIV infection status and antiretroviral therapy (ART) use. Results: Over a 7-year follow-up, 112 individuals developed CAP (90 HIV+, 22 HIV-). After multivariate adjustment, ceramides C16:0 (RR=1.40 [95% CI: 1.09-1.79]; P <0.001) and C24:1 (RR=1.32 [1.06-1.65]; P <0.001), but not ceramides C22:0 or C24:0, were significantly associated with increased risk of CAP in all participants. Ceramides C16:0 showed stronger association with CAP in HIV+ people compared to HIV- people ( Figure ), but there was no significant effect modification by HIV infection status ( P for interaction>0.05). Compared to HIV- group, plasma ceramides C16:0, C22:0 and C24:1 were significantly ( P <0.001) higher in HIV+ group. Further analyses in HIV+ group showed that ceramides were significantly ( P < 0.001) higher in people using ART than those not using ART. Conclusions: This study reported that elevated plasma ceramides, especially C16:0, are increased with ART use and associated with HIV-related atherosclerosis. Our data suggest that ceramides might be an intermediate link between HIV infection and CVD risk.