Immune activation and cardiovascular disease in chronic HIV infection

Abstract

Purpose of review: This article describes the potential contribution of immune activation in the pathogenesis of HIV-associated cardiovascular disease (CVD) - a leading cause of morbidity and mortality among HIV-positive persons with access to antiretroviral therapy (ART).

Recent findings: We review recent literature that suggests abnormalities in both adaptive and innate immunity contributes to CVD risk among persons with HIV infection. In particular, potentially atherogenic T-cell mechanisms include persistent high-level T-cell activation (and associated proinflammatory mechanisms), as well as the presence of copathogens (e.g., cytomegalovirus) providing an ongoing stimulus for cytotoxic T-cell responses. More recent data have then emphasized the potential impact of monocyte-/macrophage-mediated inflammation and injury within atherosclerotic lesions. The abnormality driving innate immune activation many not fully reverse with antiretroviral therapy, highlighting the need for interventions that target inflammation as a CVD prevention strategy.

Summary: Premature CVD among persons with HIV infection is due, in part, to persistent abnormalities in immune activation and systemic inflammation despite viral suppression. Prevention strategies for persons with HIV infection include those that target traditional CVD risk factors, as well as newer candidate treatments with potential immunomodulatory benefits.

FIGURE 1. Adaptive immunity in atherosclerosis

T and B lymphocytes may positively or negatively influence atherosclerotic plaque through direct action on lesions or through inflammatory cytokine production. Emerging observational data have linked CD8+ and CD4+ T-cell activation to subclinical vascular disease and adverse outcomes among those with HIV infection; relatively less is known about the role of T_Reg or B lymphocytes in the context of HIV disease. Reproduced with permission from Libby et al.[39]

FIGURE 2. Innate immunity in atherosclerosis

Elements of the innate immune system, particularly monocytes and macrophages, drive atherosclerosis and the inflammation that leads to unstable atherothrombotic syndromes. Current literature has demonstrated that HIV infection activates monocytes, impairs reverse cholesterol transport from foam cells, and promotes thrombus formation through platelet-monocyte interactions. Reproduced with permission from Libby et al.[39]