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The metabolic and cardiovascular consequences of obesity in persons with HIV on long-term antiretroviral therapy

Objective:This study assessed the effect of obesity on metabolic and cardiovascular disease risk factors in HIV-infected adults on antiretroviral therapy with sustained virologic suppression. Design:Observational, comparative cohort study with three group-matched arms: 35 nonobese and 35 obese HIV-infected persons on efavirenz, tenofovir and emtricitabine with plasma HIV-1 RNA less than 50 copies/ml for more than 2 years, and 30 obese HIV-uninfected controls. Patients did not have diabetes or known cardiovascular disease. Methods:We compared glucose tolerance, serum lipids, brachial artery flow-mediated dilation, carotid intima–media thickness, and soluble inflammatory and vascular adhesion markers between nonobese and obese HIV-infected patients, and between obese HIV-infected and HIV-uninfected patients, using Wilcoxon rank-sum tests and multivariate linear regression. Results:The cohort was 52% men and 48% nonwhite. Nonobese and obese HIV-infected patients did not differ by clinical or demographic characteristics. Obese HIV-uninfected controls were younger than obese HIV-infected patients and less likely to smoke (P < 0.03 for both). Among HIV-infected patients, obesity was associated with greater insulin release, lower insulin sensitivity, and higher serum high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-&agr; receptor 1 levels (P < 0.001), but similar lipid profiles, sCD14, sCD163, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, and carotid intima-media thickness and flow mediated dilation. In contrast, Obese HIV-infected patients had adverse lipid changes, and greater circulating intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and sCD14, compared with obese HIV-uninfected controls after adjusting for age and other factors. Conclusion:Obesity impairs glucose metabolism and contributes to circulating high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-&agr; receptor 1 levels, but has few additive effects on dyslipidemia and endothelial activation, in Obese HIV-infected adults on long-term antiretroviral therapy.