Coronary Artery Disease in HIV-Infected Patients: Downside of Living Longer

Abstract

Purpose of review: Introduction of combination antiretroviral therapy (ART) has increased the life expectancy of patients with HIV infection, allowing them to live longer with this chronic medical condition and consequently experiencing conditions such as cardiovascular diseases (CVDs). Several studies have investigated the increased risk of CVD in people living with HIV (PLWH). However, less is known about the exact mechanisms involved in this increased risk. Also, specific guidelines for management of CVD in PLWH have not been developed yet. In this article, we review the recent literature on the mechanisms involved in pathogenesis of CVD in PLWH, with an emphasis on coronary artery disease (CAD).

Recent findings: Although initial studies suspected the increased prevalence of traditional CVD risk factors and side effects of ART to be involved in the increased CVD risk in PLWH, recent studies have uncovered the important role of chronic persistent inflammation in this increased risk. In addition, biomarkers of inflammation have been associated with both CVD events and subclinical CAD in this population. Lastly, recent studies and ongoing clinical trials have been investigating medical interventions that aim to reduce inflammation and cardiovascular events. Different mechanisms of inflammation have been examined in PLWH, including subclinical viremia, microbial translocation, and coinfection with other pathogens such as cytomegalovirus. Although inflammatory biomarkers have been consistently associated with CVD and subclinical CVD outcomes, their prognostic value is unknown. Recent and ongoing trials are exploring the benefits of anti-inflammatory drugs, statins, and antimicrobial translocation drugs on both inflammation and CVD risk among PLWH.

Keywords: Biomarkers; Cardiovascular disease; Clinical trials; Coronary artery disease; HIV infection; Inflammation.

Fig. 1

Current paradigm of mechanisms involved in increased risk of cardiovascular disease among people living with HIV. HIV infection results in the emergence of several factors that increase cardiovascular disease (CVD) risk. Traditional CVD risk factors such as dyslipidemia, smoking, high blood pressure, and substance abuse contribute to higher CVD risk in people living with HIV (PLWH). Some antiretroviral therapies (ARTs) have been directly and indirectly (via traditional risk factors) associated with CVD risk, particularly abacavir and protease inhibitors (PIs). Chronic inflammation, in the form of increased monocyte and T cell activation, endothelial adhesion, and dysfunction and hypercoagulation, has been significantly associated with increased CVD in the general population and is more aggravated in PLWH due to (1) HIV-associated immune deficiency leading to coinfections with pathogens such as cytomegalovirus (CMV) and human herpesvirus-8 (HHV-8) that increase chronic inflammation; (2) subclinical viremia also leads to higher inflammation; (3) microbial translocation, or “leaky gut,” characterized by decreased regulatory cells and mucosal immunity (lower Th17 and CD4+ cells), disrupted gut epithelial barrier (less tight junctions and higher endothelial cell (EC) apoptosis), and persistent presence of the HIV virus in the gut; and (4) toll-like receptor (TLR) 7 and 8 activation in macrophages and dendritic cells. Early initiation and sustained use of ART has been shown to decrease chronic inflammation in PLWH