Review Article
Coronary artery disease in patients with human immunodeficiency virus infection

https://doi.org/10.1007/s12350-020-02280-4Get rights and content

Abstract

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug–drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.

Introduction

Globally, an estimated 36.7 million people were living with human immunodeficiency virus (HIV) in 2015.1 The Joint United Nations Programme on HIV/Acquired Immune Deficiency Syndrome (AIDS), UNAIDS, estimated that in 2015 about 1.2 million people were living with HIV (PLWH) in the United States with 39,000 new HIV infections that year.2 The increased life expectancy of PLWH in developed countries has been largely attributed to better access to combination antiretroviral therapy (ART)3 that has reduced AIDS related mortality and morbidity. However in PLWH, deaths and morbidity due to non-AIDS defining illnesses have been on the rise. Farahani et al. estimated that the pooled non-AIDS causes of death in PLWH in high income countries were 53 percent, and a significant number of this was from cardiovascular disease (CVD), non-AIDS malignancies and liver disease.4 In this review, we will describe in detail the pathogenesis and manifestations of cardiovascular disease that occur in PLWH, as well as a brief review of non-invasive modalities for prognosticating CAD.

Section snippets

HIV and atherosclerosis

CVD is emerging as a major public health concern in PLWH. Atherosclerosis is consistently higher among the HIV-positive population, with or without treatment, than among the HIV-negative population. Subclinical markers of atherosclerosis, such as carotid, femoral and iliac intima-thickness are greater and progress earlier in the HIV-positive population.5, 6, 7 The factors linked to atherosclerosis in PLWH are both traditional (age, diabetes mellitus, smoking, dyslipidemia, inflammation and

HIV and coronary artery disease (CAD)

The association of CAD and HIV has been well recognized for years. An increased prevalence of CAD in this high risk group may be due to various complex interactions between the virus, host and treatment. In this section of the review, we will focus on the epidemiological evidences linking HIV to CAD. We will discuss the cardiovascular effects of ART, interactions of ART with drugs used in the treatment of CAD and the current revascularization practices in HIV-positive individuals.

HIV infection

Clinical presentation and outcomes of CAD and acute coronary syndrome (ACS)

Several observational studies have evaluated the clinical presentation of CAD in HIV patients. One of the earlier studies evaluating ACS in persons with HIV showed that the HIV group was 10 years younger and had low blood pressure, lower HDL, and a lower Thrombolysis in Myocardial Infarction (TIMI) score compared with the uninfected group.98 A meta-analysis demonstrated that the most common presentation was ST-segment elevation myocardial infarction (STEMI), comprising of 57% of the CAD related

CAD in HIV-infected women

Women represent almost 25% of PLWH. Thus, it is important to understand their risk of CAD to optimize adequate prevention, screening and treatment.111 Studies have demonstrated that the relative risk of MI was greater in women with HIV (2.7-3) as compared to men (1.4) when compared with uninfected controls.43,112 The median age at the first event was significantly lower in HIV-infected women as compared with uninfected women (49.3 years versus 52.1 years) 112. Women have a higher prevalence of

Exercise tolerance testing

Exercise tolerance testing is widely used as a diagnostic test in the initial evaluation of patients with symptoms suggestive of myocardial ischemia and in persons with previously recognized coronary heart disease. The treadmill exercise electrocardiogram test is one of the most commonly used and least expensive test which has a mean sensitivity of 68% and specificity of 77%, respectively for detecting angiographically significant coronary artery disease.114 The utility of exercise testing as a

Conclusion

HIV and CAD are both global health issues which pose a significant burden to the medical community. With better and more tolerant ART, the life expectancy of HIV-positive individuals has increased. In the past 2 decades we have better understood the mechanisms that link HIV to CAD. However, we need more research to be able to target specific pathways that play crucial roles in the pathogenesis of atherosclerosis and CAD in HIV-infected individuals. Drug-drug interactions and adverse effects of

Disclosures

None of the authors have any disclosures and conflicts of interest pertinent to this topic.

References (166)

  • WHO | 10 facts on HIV/AIDS....
  • United States of America....
  • FarahaniM et al.

    Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: A systematic review and meta-analysis

    Int J STD AIDS.

    (2017)
  • ThiébautR et al.

    Change in atherosclerosis progression in HIV-infected patients: ANRS Aquitaine Cohort, 1999-2004

    AIDS Lond Engl.

    (2005)
  • MerciéP et al.

    Carotid intima-media thickness is slightly increased over time in HIV-1-infected patients

    HIV Med.

    (2005)
  • PeriardD et al.

    High prevalence of peripheral arterial disease in HIV-infected persons

    Clin Infect Dis Off Publ Infect Dis Soc Am.

    (2008)
  • SinghaniaR et al.

    Lipodystrophy in HIV patients: Its challenges and management approaches

    HIV AIDS (Auckl).

    (2011)
  • SabinCA et al.

    Conventional cardiovascular risk factors in HIV infection: How conventional are they?

    Curr Opin HIV AIDS.

    (2008)
  • ShresthaS et al.

    HIV, inflammation, and calcium in atherosclerosis

    Arterioscler Thromb Vasc Biol.

    (2014)
  • GuiT et al.

    Diverse roles of macrophages in atherosclerosis: From inflammatory biology to biomarker discovery

    Mediators Inflamm.

    (2012)
  • ChomaratP et al.

    IL-6 switches the differentiation of monocytes from dendritic cells to macrophages

    Nat Immunol.

    (2000)
  • TedguiA et al.

    Cytokines in atherosclerosis: Pathogenic and regulatory pathways

    Physiol Rev.

    (2006)
  • StoneSF et al.

    Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART

    HIV Med.

    (2002)
  • KullerLH et al.

    Inflammatory and coagulation biomarkers and mortality in patients with HIV infection

    PLoS Med.

    (2008)
  • HanssonGK

    Inflammation, atherosclerosis, and coronary artery disease

    N Engl J Med.

    (2005)
  • JonesKL et al.

    Chemokine receptor CCR5: From AIDS to atherosclerosis

    Br J Pharmacol.

    (2011)
  • DeanM et al.

    Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study

    Science.

    (1996)
  • RaoRM et al.

    Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall

    Circ Res.

    (2007)
  • SöderquistB et al.

    Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients with Staphylococcus aureus bacteraemia with or without endocarditis

    Clin Exp Immunol.

    (1999)
  • CroweSM et al.

    The macrophage: The intersection between HIV infection and atherosclerosis

    J Leukoc Biol.

    (2010)
  • LeyK et al.

    Monocyte and macrophage dynamics during atherogenesis

    Arterioscler Thromb Vasc Biol.

    (2011)
  • SwinglerS et al.

    HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages

    Nat Med.

    (1999)
  • DressmanJ et al.

    HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages

    J Clin Invest.

    (2003)
  • TabasI

    The role of endoplasmic reticulum stress in the progression of atherosclerosis

    Circ Res.

    (2010)
  • OyadomariS et al.

    Roles of CHOP/GADD153 in endoplasmic reticulum stress

    Cell Death Differ.

    (2004)
  • TabasI et al.

    Macrophage apoptosis in advanced atherosclerosis

    Ann N Y Acad Sci.

    (2009)
  • ErdmannF et al.

    Interaction of calmodulin with Sec61α limits Ca2+ leakage from the endoplasmic reticulum

    EMBO J.

    (2011)
  • MekahliD et al.

    Endoplasmic-reticulum calcium depletion and disease

    Cold Spring Harb Perspect Biol.

    (2011)
  • NormanJP et al.

    HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization

    PLoS ONE.

    (2008)
  • WalliR et al.

    Impaired glucose tolerance and protease inhibitors

    Ann Intern Med.

    (1998)
  • DeverLL et al.

    Hyperglycemia associated with protease inhibitors in an urban HIV-infected minority patient population

    Ann Pharmacother.

    (2000)
  • GrunfeldC et al.

    Contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors

    Circulation.

    (2008)
  • YoungJ et al.

    Lipid profiles for antiretroviral-naive patients starting PI- and NNRTI-based therapy in the Swiss HIV cohort study

    Antivir Ther.

    (2005)
  • IngleSM et al.

    Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients

    Clin Infect Dis Off Publ Infect Dis Soc Am.

    (2014)
  • PaisibleA-L et al.

    HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction

    J Acquir Immune Defic Syndr

    (2015)
  • SilverbergMJ et al.

    Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care

    J Acquir Immune Defic Syndr.

    (2014)
  • DurandM et al.

    Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: A cohort and nested case-control study using Québec’s public health insurance database

    J Acquir Immune Defic Syndr

    (2011)
  • LangS et al.

    Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population

    AIDS Lond Engl.

    (2010)
  • IloejeUH et al.

    Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients

    HIV Med.

    (2005)
  • CoplanPM et al.

    Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: An analysis of four different protease inhibitors

    AIDS Res Hum Retroviruses.

    (2003)
  • Cited by (0)

    The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

    The authors have also provided an audio summary of the article, which is available to download as ESM, or to listen to via the JNC/ASNC Podcast.

    View full text