Since the introduction of antiretroviral therapy (ART) in the mid-1990s, human immunodeficiency virus (HIV) has transformed into a chronic disease with decreased mortality rates. With improved life expectancy, these patients are constantly at risk of being exposed to long-term non-acquired immunodeficiency syndrome (AIDS)-related chronic comorbid diseases such as cardiovascular disease (CVD). Studies have shown that HIV infection poses the increased risk of myocardial infarction (MI), heart failure, and stroke.¹,²,³ The recent data show the rates of death because of non-HIV attributable causes, such as CVD, have increased in comparison to HIV attributable causes.⁴ The underlying mechanism for augmented HIV-associated CVD risk is not clear; however, it extends beyond the traditional risk factors for atherosclerosis. So far, our understanding of this high-risk group is principally based on the observational data, and the randomized controlled studies have largely been underpowered to identify clinical CVD outcomes. This chapter summarizes the epidemiology, pathophysiology, clinical signs and symptoms, angiographic findings, management including ART, and prevention of CVD in HIV-infected patients.

Although the mechanism of increased CVD in HIV-infected patients is incompletely understood and is likely multifactorial, its core is thought to be progressive atherosclerosis. The evidence suggests that onset of atherosclerosis is driven by activation of innate immune system that plays an important role in the pathogenesis. One of the underlying mechanisms is believed to be aberration of intestinal barrier allowing lipopolysaccharide to enter systemic circulation leading to immune system activation.¹² Lipopolysaccharide, a microbial product, is considered as an essential marker of microbial translocation, which binds with lipopolysaccharide binding protein (LBP) and transfers into soluble CD14, leading to nuclear factor-kappa B (NF-κB) activation and cytokine production.¹²,¹³ Soluble CD163, another circulating marker expressed on monocytes and macrophages and has been independently associated with noncalcified plaques among asymptomatic young men in previous studies, is meaningfully correlated to the extent of arterial inflammation in HIV infection.¹⁴ Both microbial translocation and macrophage activation (soluble CD14 and soluble CD163) are associated with subclinical atherosclerosis progression in HIV patients.¹⁵ Furthermore, the activation of adaptive immune system occurs early during acute HIV infection through the T-cell receptors on both CD4 and CD8 after the initial exposure to the virus.¹⁶ Persistent T-cell activation leads to exhaustion and senescence of the immune system leading to declined naive CD4 and CD8 T-cell numbers. This eventually leads to a gradual depletion of total CD4 counts that has been independently linked to increased risk of atherosclerosis.¹⁷

The clinical presentation of CVD in HIV-infected patients could range from silent ischemia to ACS. Based on published data, the most common presentation was ST-elevation MI, followed by non-ST-elevation MI and unstable angina.²⁸,²⁹ HIV patients tend to be on average a decade younger than the uninfected individuals and are more likely to be young men (<50 years), smoker, having dyslipidemia, with lengthier duration (>8 years) of HIV, and taking ART.²⁸

HIV also poses increased risk of heart failure independent of MI. A cohort study in VA population of approximately 98,000 patients showed HIV-infected patients are at increased risk of heart failure with persevered ejection fraction (HFpEF), borderline HFpEF, and heart failure with reduced ejection fraction (HFrEF).¹ HFrEF in these patients could manifest even decades earlier than would be expected in the general population.¹ A recent retrospective Veterans Affairs cohort study demonstrated a higher risk of hospitalization and mortality in HIV-positive patients, and worse outcomes were seen in individuals with higher viral count, lower CD4 count, and decreased ejection fraction.³⁰ A systematic review and meta-analysis showed these patients are at increased risk of
both ischemic (HR 1.27, 1.15-1.39) and hemorrhagic stroke (HR 2.20, 1.61-3.02).² Immunosuppression and high viral load are considered as independent risks for ischemic stroke and peripheral arterial disease in this population.³¹ Taken together, presence of HIV infection itself should be considered as a vascular risk factor, and future strategies should be tailored to reduce the risk and prevention of vascular events in this population.²