Atherosclerosis is primarily a disease of inflammation. When the lining of the arterial wall (the endothelium) becomes inflamed, lipid laden foam cells are promoted and drive progression from asymptomatic fatty streaks to pathological atherosclerotic plaques. Foam cells are generated when activated monocytes ingest cholesterol, take up residence in the endothelial wall and then secrete inflammatory cytokines and chemokines to promote ongoing inflammation. Monocytes from people with HIV infection are more prone to transform into foam cells ^[43], and higher levels of monocyte-derived molecules, such as soluble CD14 (sCD14), have been associated with HIV infection ^[44]. Furthermore, elevated plasma levels of sCD14 and other markers of monocyte activation have been shown to predict mortality among people with HIV infection ^[45], as well as in the general population ^[46].

It has been proposed that acute HIV infection leads to CD4⁺ T-cell depletion in the gut and loss of mucosal integrity (the so-called “leaky gut syndrome”), thus allowing microbial products, particularly lipopolysaccharide, to leak into the systemic circulation where it stimulates monocytes and promotes inflammation ^[47]. More recent studies suggest more complex underlying mechanisms ^[48,49], and there is also emerging evidence that markers of monocyte activation are reduced in the context of integrase inhibitor therapy ^[50,51]. The impact on CVD risk remains to be determined, although it is an interesting possibility that choice of ART may have an impact on inflammatory pathways that are important for the development of atherosclerotic disease.