HIV and Cardiovascular Disease: We Need a Mechanism, and We Need a Plan

W ith the advent of antiretroviral therapy (ART) and increased survival, HIV-infected people are now at risk for diseases of aging including cardiovascular disease (CVD). In the ART era, multiple large cohort studies have found that HIV infection is associated with an increased risk of acute myocardial infarction (AMI), ischemic stroke, and heart failure. Although total mortality has been decreasing for a decade among HIV-infected people, CVD mortality has significantly increased over that same time period. The underlying mechanism driving excess CVD risk is not clear but likely involves a combination of factors including the virus itself, the side effects of ART, and the burden of traditional risk factors for coronary heart disease (eg, smoking) and nontraditional risk factors (eg, hepatitis C, substance use or abuse). In addition, some evidence suggests that HIV-infected people are less likely than uninfected persons to receive treatment for some CVD risk factors and for procedures related to acute coronary syndrome. Taken together, these data suggest that health care disparities may also contribute to the increased CVD morbidity and mortality among HIV-infected people. In the early part of the ART era, observational studies reported that ART is an important risk factor for CVD in HIVinfected people. In fact, the concern about excess risk of CVD associated with ART was one of the findings that led to the Strategies for Management of Antiretroviral Therapy (SMART), a randomized controlled trial that examined CD4 cell count–guided interruption of ART (ie, less ART) versus continuous ART (ie, less HIV virus) and the risk of opportunistic infections, death, and other adverse events including CVD. SMART clearly demonstrated that episodic ART did not reduce the risk of opportunistic infections, death, or adverse events, including CVD, that were associated with ART. Moreover, the results suggested that unsuppressed HIV virus plays a larger role in the risk of CVD events than ART. Coronary heart disease is largely a function of progressive atherosclerosis, which involves inappropriate lipid metabolism and activation of the innate and adaptive immune systems in the arterial wall. HIV-infected people can experience T cell depletion related to the HIV virus and dyslipidemia caused by ART and have increased levels of inflammation, monocyte activation, and altered coagulation compared with uninfected people. It follows that HIV infection and ART treatment may independently increase the risk of coronary heart disease by progressive atherosclerosis. Unfortunately, initial reports examining the cross-sectional association between HIV infection and subclinical atherosclerosis have been inconsistent. A 2009 meta-analysis found that HIV status was associated with increased carotid intima– media thickness (cIMT) but not carotid plaque or coronary artery calcium. These inconsistent results may have been a consequence of the significant heterogeneity in methods and differential prevalence of CVD risk factors by HIV status across studies. Similarly, longitudinal studies examining HIV infection and subclinical atherosclerosis among children and adults have reported inconsistent results. Among children without a significant burden or duration of risk factors for coronary heart disease, those who were ART-na€ıve had increased cIMT, whereas those who were ART-exposed had similar cIMT compared with children without HIV infection. A 144week longitudinal study described higher cIMT at baseline among HIV-infected children but similar levels compared with uninfected children by study end. Among adults, the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study reported that HIV infection was associated with higher incidence but not progression of coronary artery calcium. Hsue et al also reported higher rates of cIMT progression in HIV-infected versus uninfected people, with greater differences observed in the carotid bifurcation The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Vanderbilt University Medical Center and the Geriatric Research Education and Clinical Care Service, VA Tennessee Valley Health Care System, Nashville, TN. Correspondence to: Matthew S. Freiberg, MD, MSc, Cardiovascular Medicine Division, Vanderbilt UniversityMedical Center, Nashville VAMC, 2525West End, Suite 300-A, Nashville, TN 37203. E-mail: [email protected] J Am Heart Assoc. 2016;5:e003411 doi: 10.1161/JAHA.116.003411. a 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.