Elevated Plasma Ceramides Are Associated With Antiretroviral Therapy Use and Progression of Carotid Artery Atherosclerosis in HIV Infection

• DOI: 10.1161/circulationaha.118.037487
• Publication Date: 2019-02-14T10:09:02Z
• Authors: Wei Zhao; Xueyin Wang; Amy A. Deik; David B. Hanna; Tao Wang; Sabina A. Haberlen; Sanjiv J. Shah; Jason M. Lazar; Howard N. Hodis; Alan L. Landay; Bing Yu; Deborah Gustafson; Kathryn Anastos; Wendy S. Post; Clary B. Clish; Robert C. Kaplan; Qibin Qi
• Keywords: Adult; Carotid Artery Diseases; Inflammation; Male; 0301 basic medicine; HIV Infections; Comorbidity; HIV Protease Inhibitors; Middle Aged; Ceramides; Monocytes; 3. Good health; 03 medical and health sciences; Anti-Retroviral Agents; Socioeconomic Factors; Risk Factors; Disease Progression; Humans; Multicenter Studies as Topic; Female; Prospective Studies; Follow-Up Studies

Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels association with subclinical disease risk among HIV-infected individuals. Plasma 4 species (C16:0, C22:0, C24:0, C24:1) were measured 398 women (73% HIV+) 339 men (68% without carotid artery plaques at baseline from Women's Interagency Study Multicenter AIDS Cohort Study. We examined associations between plasma ceramides plaque formation, assessed by repeated B-mode ultrasound imaging over a median 7-year follow-up. C16:0, C24:1 significantly higher individuals compared those (all P<0.001), further analysis indicated that elevated associated antiretroviral therapy use, particularly protease inhibitor P<0.001). All highly correlated each other ( r=0.70-0.94; all P<0.001) total-cholesterol r=0.42-0.58; low-density lipoprotein cholesterol r=0.24-0.42; levels. Of note, C16:0 ceramides, rather than C22:0 C24:0 more closely specific monocyte activation inflammation markers (eg, r=0.30 soluble CD14; surface CD4+ T-cell activation. A total 112 participants developed 7 years, increased (relative [95% CI]=1.55 [1.29, 1.86] 1.51 [1.26, 1.82] per standard deviation increment, respectively; both after adjusting for demographic behavioral factors. After adjustment factors immune markers, these attenuated but remained significant. The results consistent HIV-uninfected participants. In 2 cohorts, correlating inflammation, use progression atherosclerosis.