Whether HIV infection and antiretroviral (ARV) therapy are both independent coronary risk factors in people living with HIV (PLWHIV) remains controversial.1 However, overall, studies suggest that HIV-associated atherosclerosis is determined by advanced HIV disease, high-level viremia and exposure to certain ARV drugs, as well as chronic inflammation.2

HIV infection and coronary artery disease (CAD)

Atherosclerosis in people infected with HIV may develop due to HIV infection itself and/or traditional causes/risk factors.3–6 Recent data suggest that HIV infection, if untreated, amplifies pro-atherogenic mechanisms such as immune activation, inflammation, coagulation and changes to lipoprotein particles.7

  • Even after adjustment for traditional risk factors, some studies have suggested an association between HIV infection and higher carotid intima-medial thickness (CIMT, a measure of pre-clinical/sub-clinical atherosclerosis)8,9
  • Although it is not fully understood how HIV may promote CAD, various mechanisms have been explored.2 Chronic infection, inflammation and HIV-mediated disruption of immune balance have the potential to alter vascular structure and function1
  • HIV may affect lipid processing and delivery to vessel walls, as suggested by the association of lower CD4+ lymphocyte counts with lower levels of apolipoprotein B and smaller low-density lipoprotein cholosterol (LDL-C) particles.2
  • HIV infection has also been associated with chronic inflammation, for example caused by infection with Chlamydia pneumoniae and cytomegalovirus, which in turn may promote atherosclerosis.10 In one study assessing the role of chronic inflammation, higher CIMT was demonstrated in HIV-infected patients compared with healthy controls.11 
  • HIV could potentially have direct effects on the myocardium and vascular endothelium, but there are limited data on direct cellular infection.12

Highly active ARV therapy (HAART) and CAD

Pro-atherogenic mechanisms associated with HIV infection may be attenuated, although incompletely, by ARV-mediated virological suppression.7 However use of ARV regimens is associated with metabolic effects that may increase (CV) risk.7

Atherosclerosis may be associated with the metabolic side effects that have been observed with the use of protease inhibitors (PIs), including insulin resistance, diabetes mellitus, hypertension, abnormalities in lipid metabolism and fat redistribution.8,12,13  

  • Alterations in lipid metabolism may influence plaque formation.12 Endothelial and myocardial function may also be affected by associated metabolic changes, including insulin resistance and fat redistribution12
  • However, some studies have shown no effect of PIs on coronary heart disease (CHD) in PLWHIV.10,14 In one analysis, the association between CHD rates and PI use was significantly attenuated when data were adjusted for dyslipidaemia12
  • Dyslipidaemia will be covered as a separate medical condition within this website (upcoming), refer to this or to guidelines from the Infectious Disease Society of America (IDSA)

An increase in vascular age, as measured by the amount of coronary artery calcium (CAC), has been demonstrated in mid-aged patients (mean age 48 years) with stable HIV-infection receiving ARV therapy. In this study, increased vascular age was found to be frequent among HIV-infected patients and appeared to be associated with an increased CD4+ cell count.15 

Endothelial dysfunction, HIV, HAART and CAD

Endothelial dysfunction may be an early manifestation of atherosclerosis:12

  • endothelial dysfunction is present in ARV therapy-naïve HIV-infected patients, although data on direct infection of the vasculature are limited
  • in general, HAART only somewhat improves endothelial function in HIV-infected patients, which may be due to negative effects of specific ARV drugs, viral protein-mediated endothelial activation, or chemokine dysregulation with activation of macrophages, smooth muscle cells and enhanced atheroma formation
  • data suggest that the use of regimens including indinavir may worsen endothelial function
    • potential mechanisms for this effect include reduction in nitric oxide production or release, increases in reactive oxygen species, impairment of cholesterol efflux from foam cells and increased macrophage cholesterol ester accumulation through up-regulation of the CD36 scavenger receptor
  • specific nucleoside reverse transcriptase inhibitors (NRTIs), including stavudine and zidovudine, may also increase superoxide production in experimental models

Acute coronary syndromes (ACS)

Although ACS have different clinical presentations, they share a common pathophysiology:16

  • atherosclerotic plaque rupture or erosion represents the basic pathophysiological mechanism in most ACS, demonstrated by pathological, angioscopic and biological observations
  • plaque rupture or erosion may have differing degrees of superimposed thrombosis and distal embolisation, resulting in myocardial under-perfusion


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