Why is HIV considered a risk factor for atherosclerosis?

Why HIV is Considered an Atherosclerosis Risk Factor

HIV infection is classified as an atherosclerosis risk factor because it causes accelerated atherosclerosis through three distinct mechanisms: chronic inflammation and immune activation from the virus itself, adverse metabolic effects from antiretroviral therapy, and a higher prevalence of traditional cardiovascular risk factors. 1

Primary Mechanisms of HIV-Associated Atherosclerosis

Direct Viral Effects

• HIV infection itself drives chronic immune activation and inflammation that directly promotes atherosclerosis progression, independent of antiretroviral therapy. 1
• The virus causes prolonged immune activation that mediates atherosclerotic plaque progression, instability, erosion, and rupture. 1
• Patients with HIV have a 1.5- to 2-fold excess risk of atherosclerotic cardiovascular disease compared to age- and sex-matched controls, even when viremia is controlled. 1
• Higher CD4 cell counts and lower HIV RNA levels are associated with lower atherosclerotic cardiovascular disease risk, demonstrating the direct relationship between viral control and cardiovascular outcomes. 1

Antiretroviral Therapy Effects

• Antiretroviral medications, particularly older protease inhibitors, cause adverse lipid changes including elevated triglycerides, increased LDL cholesterol, and decreased HDL cholesterol. 1
• Long-term antiretroviral therapy use is independently associated with increased myocardial infarction risk. 1
• Protease inhibitors interfere with cholesterol metabolism and can directly damage endothelial cells, smooth muscle cells, and macrophages. 2
• Specific agents like boosted darunavir and abacavir have been associated with increased cardiovascular events. 1

Traditional Risk Factor Amplification

• HIV-infected patients have 2-3 times higher smoking rates than the general population. 1
• The population experiences higher prevalence of hypertension, dyslipidemia, insulin resistance, diabetes, and body composition changes. 1
• Traditional cardiovascular risk calculators consistently underestimate actual atherosclerotic cardiovascular disease risk in HIV patients by 50% or more, particularly in women and Black individuals. 1

Clinical Evidence of Accelerated Atherosclerosis

Cardiovascular Event Data

• The SMART trial demonstrated that episodic antiretroviral therapy (versus continuous therapy) increased myocardial infarction rates from 0.8 to 1.3 per 100 person-years. 1
• HIV-infected individuals have approximately 50% increased risk of cardiovascular death compared to uninfected controls. 1
• The risk of myocardial infarction in HIV patients is comparable to that of adults with diabetes mellitus or individuals 10 years older without HIV. 1

Subclinical Atherosclerosis Markers

• Studies demonstrate increased carotid intima-media thickness in HIV-infected patients, with prevalence of subclinical atherosclerosis ranging from 14-24% depending on antiretroviral therapy status. 3
• Coronary artery calcification is increased in HIV-infected patients compared to controls. 1
• Endothelial dysfunction, the strongest predictor being protease inhibitor use, is significantly impaired in HIV patients. 1

Inflammatory and Metabolic Pathways

Chronic Inflammation

• Elevated inflammatory biomarkers including C-reactive protein, interleukin-6, and TNF-alpha are consistently found in HIV patients and correlate with atherosclerosis progression. 3, 4, 5
• Inflammation persists even with viral suppression, contributing to ongoing cardiovascular risk. 4
• Monocyte chemoattractant protein-1 and oxidized LDL levels are independently associated with subclinical atherosclerosis in HIV patients with otherwise low calculated risk. 6

Lipid Abnormalities

• The most common lipid phenotype in HIV infection is elevated triglycerides with low HDL cholesterol. 1
• HIV causes dyslipidemia through direct viral effects and chronic immune activation, independent of antiretroviral therapy. 2
• Antiretroviral therapy, especially protease inhibitors, exacerbates dyslipidemia through interference with cholesterol metabolism. 2

Clinical Implications

Risk Assessment Limitations

• Standard Framingham risk scores significantly underestimate cardiovascular risk in HIV patients, showing weak agreement with actual subclinical atherosclerosis (kappa = 0.229). 6
• Among patients classified as "low risk" by Framingham scoring, 56% actually had subclinical atherosclerosis. 6
• The 2018 ACC/AHA guidelines formally recognize HIV as a "risk-enhancing factor" that should guide cholesterol management decisions. 1

Treatment Considerations

• Continuous antiretroviral therapy is essential to decrease cardiovascular event risk, as treatment interruption significantly increases myocardial infarction rates. 1
• Newer generation antiretroviral regimens (such as dolutegravir-based therapy) have more favorable lipid profiles and should be preferentially selected. 1
• Based on the REPRIEVE trial, moderate-intensity statin therapy is recommended for HIV patients aged 40-75 years with atherosclerotic cardiovascular disease risk ≥5%, showing 36% reduction in major adverse cardiovascular events. 1

Common Pitfalls to Avoid

• Do not rely solely on traditional risk calculators in HIV patients, as they systematically underestimate actual cardiovascular risk. 1, 6
• Avoid lovastatin or simvastatin with protease inhibitors due to CYP3A4 interactions that increase rhabdomyolysis risk. 1
• Do not overlook the need for multidisciplinary care involving infectious disease specialists when managing cardiovascular risk in HIV patients. 1
• Consider switching from abacavir-containing regimens in patients with or at high cardiovascular risk due to its association with increased cardiovascular events. 1