Mechanisms of Cardiovascular Disease in the Setting of HIV Infection

Abstract

Although the initial reports of increased cardiovascular (CV) disease in the setting of advanced AIDS were reported approximately 30 years ago, advances in antiretroviral therapy and immediate initiation of therapy on diagnosis have transformed what was once a deadly infectious disease into a chronic health condition. Accordingly, the types of CV diseases occurring in HIV have shifted from pericardial effusions and dilated cardiomyopathy to atherosclerosis and heart failure. The underlying pathophysiology of HIV-associated CV disease remains poorly understood, partly because of the rapidly evolving nature of HIV treatment and because clinical endpoints take many years to develop. The gut plays an important role in the early pathogenesis of HIV infection as HIV preferentially infects CD4+ T cells, 80% of which are located in gut mucosa. The loss of these T cells damages gut mucosa resulting in increased gut permeability and microbial translocation, which incites chronic inflammation and immune activation. Antiretroviral therapy does not cure HIV infection and immune abnormalities persist. These abnormalities correlate with mortality and CV events. The effects of antiretroviral therapy on CV risk are complex; treatment reduces inflammation and other markers of CV risk but induces lipid abnormalities, most commonly hypertriglyceridemia. On a molecular level, monocytes/macrophages, platelet reactivity, and immune cell activation, which play a role in the general population, may be heightened in the setting of HIV and contribute to HIV-associated atherosclerosis. Chronic inflammation represents an inviting therapeutic target in HIV, as it does in uninfected persons with atherosclerosis.