Dyslipidemia and cardiovascular risk in human immunodeficiency virus infection

Abstract

The pathogenesis of atherosclerosis in human immunodeficiency virus (HIV)-infected individuals is incompletely understood and appears to be multifactorial. Proatherogenic changes in blood and tissue lipids are associated with an increased risk of cardiovascular disease among HIV-infected subjects, and these changes may be both quantitative (dyslipidemia) and qualitative. In view of the pivotal role of dyslipidemia in the process of atherosclerosis, the increased incidence of dyslipidemia in HIV-infected individuals, and the emerging role of lipid abnormalities in systemic pathophysiologic processes such as immune activation, we review the contributions of dyslipidemia to cardiovascular risk in HIV infection.

Keywords: Antiretroviral therapy; Cardiovascular risk; Dyslipidemia; Human immunodeficiency virus.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Fig. 1

PIs may modify lipoprotein metabolism through multiple mechanisms. PIs directly stimulate the biosynthesis of triglycerides in hepatic cells and may also directly modify the metabolism of lipoproteins by binding to cellular receptors, reducing lipolysis and by regulating expression of key genes involved in the regulation of metabolic pathways in adipocytes and hepatocytes. CRABP-1, cellular retinoic acid-binding protein 1; LRP, low-density lipoprotein receptor protein; PPARs, peroxisome proliferator-activated receptors; SREBPs, sterol regulatory element-binding proteins.

Fig. 2

Factoring influencing dyslipidemia and CVD risk in HIV. ART directly alters lipid metabolism and may increase the risk of insulin resistance (1). The lipid effects of ART include elevated triglycerides and for some agents elevations in TC. The elevations in triglycerides may also contribute to insulin resistance and to CVD risk (2). HIV replication per se increases immune activation and may have a direct effect on CVD risk (3). In addition HIV replication may indirectly alter HDL function via indirect effects on inflammation. These altered lipids may have direct and indirect immunoregulatory effects and induce further activation of immune cells (T cells and monocytes/macrophages), which may further increase systemic inflammation. Inflammation also contributes to insulin resistance, which, in turn, may increase CVD risk. Thus, there are complex interactions between these pathophysiologic processes that are at least partially driven by altered lipids that are formed during HIV infection and that may directly or indirectly contribute to increased CVD in HIV-infected subjects. TG, triglycerides.