Imaging atherosclerotic burden and inflammation: insights into the spectrum of atherosclerotic disease in HIV.

HIV disease, left inadequately treated, leads to an inexorable decline in immune function resulting in AIDS and ultimately in death from opportunistic infections. However, advances in treatment of HIV have resulted in a dramatic reduction in AIDS-related mortality. With the widespread use of highly active antiretroviral therapy (HAART), HIV infection has been transformed to a chronic disease associated with longterm viral suppression but at the cost of an increase in atherothrombotic diseases. Hence currently there is substantial interest in developing a better understanding of the mechanisms underlying the increased risk of atherothrombosis in HIV disease. While HIV infection is characterized by a decline of peripheral blood CD4? T cells, a paradoxical chronic immune activation of T cells and monocytes is routinely seen in virally suppressed HIV disease. Multiple studies in HIV-infected individuals show that this persistently heightened state of immune activation likely contributes to the increased incidence of atherosclerosis, itself a chronic inflammatory condition. Numerous potential causes may contribute to this chronic immune activation, including increased microbial translocation from the gut due to CD4? T lymphocytes depletion, persistent low-level viral replication, increased levels of lipopolysaccharide (LPS), sCD14, HIV gene products, and CMV-specific T-cell activation 12 among other mechanisms. In this regard, an increasing number of studies have begun to assess the relationship between atherosclerosis and immune activation in HIV-infected individuals. Recent studies by our group and others have shown substantial increases in subclinical coronary plaque. Using CT angiography, we have observed increases in non-calcified plaque volume and vulnerable plaque features in association with sCD163 an immune activation marker, indicative of monocyte activation. In a large study of over 700 HIV-infected patients and control subjects in the MACS cohort patients, Post et al similarly demonstrated increased non-calcified plaque. In a follow-up analysis, sCD163 was shown to increase in association with overall plaque indices, again using CTA. These studies support the notion, across a broad range of patients with HIV infection, (including elite controllers who have well controlled viremia without ART), that immune activation is increased in HIV, and is associated with increased coronary atherosclerotic indices. Additionally, numerous studies have shown that HIV infection is associated with an increase in extracoronary atherosclerosis, such as can be demonstrated by measurement of carotid intima-media thickness (cIMT). Hsue et al demonstrated that cIMT is greater in HIV patients than in age-matched control subjects and progresses much more rapidly than in individuals without HIV infection. The severity of carotid atherosclerosis seen in treated HIV infection (as IMT) correlates with markers of immune activation. Others have shown that the rate of progression of cIMT in HIV is predicted by markers of immune activation and Reprint requests: Ahmed Tawakol, MD, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; atawakol@partners.org J Nucl Cardiol 2015;22:381–4. 1071-3581/$34.00 Copyright 2014 American Society of Nuclear Cardiology.