HIV infection and coronary heart disease: mechanisms and management

Abstract

Antiretroviral therapy has largely transformed HIV infection into a chronic disease condition. As such, physicians and other providers caring for individuals living with HIV infection need to be aware of the potential cardiovascular complications of HIV infection and the nuances of how HIV infection increases the risk of cardiovascular diseases, including acute myocardial infarction, stroke, peripheral artery disease, heart failure and sudden cardiac death, as well as how to select available therapies to reduce this risk. In this Review, we discuss the epidemiology and clinical features of cardiovascular disease, with a focus on coronary heart disease, in the setting of HIV infection, which includes a substantially increased risk of myocardial infarction even when the HIV infection is well controlled. We also discuss the mechanisms underlying HIV-associated atherosclerotic cardiovascular disease, such as the high rates of traditional cardiovascular risk factors in patients with HIV infection and HIV-related factors, including the use of antiretroviral therapy and chronic inflammation in the setting of effectively treated HIV infection. Finally, we highlight available therapeutic strategies, as well as approaches under investigation, to reduce the risk of cardiovascular disease and lower inflammation in patients with HIV infection.

Fig. 1 |. Overview of changes in HIV treatment and HIV-associated cardiovascular diseases.

The types of cardiovascular complications associated with HIV infection have changed in the pre-antiretroviral therapy (ART) and ART eras and are likely to continue evolving in the future as new medications and treatment approaches emerge. In the pre-ART era, dilated cardiomyopathy and pericardial effusions were the most commonly reported cardiovascular issues in patients infected with HIV^,. After the introduction of protease inhibitors (PIs) in the late 1990s, atherosclerotic complications including myocardial infarction were described^,. More recently, reports of heart failure and rhythm abnormalities are now emerging in the setting of HIV infection^,. In the future, among individuals with access to ART, HIV infection will be a chronic disease state with increased risk of coronary artery disease. CCR5, CC-chemokine receptor 5; NNRTI, non-nucleoside reverse-transcriptase inhibitor ; NRTI, nucleoside reverse-transcriptase inhibitor.

Fig. 2 |. Pathophysiology and management of HIV-associated atherosclerotic cardiovascular disease.

Schematic representation of the effects of HIV infection (in red) and the available strategies (in green), as well as approaches under investigation (in purple), for reducing the risk of atherosclerotic cardiovascular disease (ASCVD) and chronic inflammation in this patient population. In the setting of HIV infection, the increased microbial translocation from the gut, the continued HIV viral replication and the HIV-induced immunodeficiency, along with traditional ASCVD risk factors, contribute to immune cell activation and chronic inflammation. HIV-specific interventions to reduce the risk of ASCVD include strategies targeted at co-infections (such as Cytomegalovirus (CMV) infection), use of newer antiretroviral therapies (ARTs) and intensification of ART. Strategies aimed at eradicating the HIV infection are under investigation. Treatments targeting traditional ASCVD risk factors, such as hypertension, diabetes mellitus, smoking and metabolic syndrome, are also critical for reducing the risk of ASCVD in patients with HIV infection. Use of anticoagulants, β-blockers, angiotensin-converting enzyme (ACE) inhibitors and LDL cholesterol (LDL-C)-lowering agents (such as statins and PCSK9 inhibitors) reduce the risk of ASCVD in patients with cardiovascular disease without HIV infection and might, therefore, be useful in reducing the risk of HIV-associated ASCVD. Finally , strategies to lower inflammation, such as canakinumab, which has been reported to reduce cardiovascular events significantly in a non-HIV patient population, might also reduce the risk of HIV-associated ASCVD.