How does Human Immunodeficiency Virus (HIV) affect cardiovascular disease?

How HIV Affects Heart Disease

HIV infection significantly increases cardiovascular disease risk through multiple mechanisms: the virus itself drives chronic inflammation and immune activation that accelerates atherosclerosis, antiretroviral therapy causes adverse metabolic effects, and HIV patients have 1.5- to 2-fold excess risk of cardiovascular events compared to uninfected individuals even with controlled viremia. 1, 2

Primary Pathophysiologic Mechanisms

Direct Viral Effects on Cardiovascular System

• HIV infection causes persistent immune activation and chronic inflammation that directly promotes atherosclerotic plaque progression, instability, erosion, and rupture, independent of antiretroviral therapy. 2, 3
• Higher CD4 cell counts and lower HIV RNA levels correlate with lower atherosclerotic cardiovascular disease risk, demonstrating that viral control directly impacts cardiovascular outcomes. 2
• Even with effective antiretroviral therapy, inflammatory markers remain elevated compared to uninfected controls, contributing to accelerated atherosclerosis. 4, 5
• The SMART trial definitively showed that episodic antiretroviral therapy (versus continuous therapy) increased myocardial infarction rates from 0.8 to 1.3 per 100 person-years, proving that viral suppression is cardioprotective. 2

Antiretroviral Therapy-Related Cardiovascular Effects

• Antiretroviral medications, particularly older protease inhibitors, cause adverse lipid changes including elevated triglycerides, increased LDL cholesterol, and decreased HDL cholesterol. 2
• Long-term antiretroviral therapy use is independently associated with increased myocardial infarction risk. 2
• Specific agents like boosted darunavir and abacavir have been associated with increased cardiovascular events. 2
• The most common lipid phenotype in HIV infection is elevated triglycerides with low HDL cholesterol. 2

Amplification of Traditional Risk Factors

• HIV-infected patients have 2-3 times higher smoking rates than the general population. 2
• The population experiences higher prevalence of hypertension, dyslipidemia, insulin resistance, diabetes, and body composition changes. 1, 2
• Traditional cardiovascular risk factors (cigarette smoking, hypertension, metabolic syndrome, dyslipidemia) combine with HIV-specific mechanisms to compound cardiovascular risk. 1

Clinical Manifestations and Risk Quantification

Magnitude of Increased Risk

• HIV-infected individuals have approximately 50% increased risk of cardiovascular death compared to uninfected controls. 2
• The risk of myocardial infarction in HIV patients is comparable to that of adults with diabetes mellitus or individuals 10 years older without HIV. 2
• Disease progression may be accelerated compared with the general population. 1

Subclinical Cardiovascular Disease

• Coronary artery calcification is increased in HIV-infected patients compared to controls. 2
• Endothelial dysfunction is significantly impaired in HIV patients, with protease inhibitor use being the strongest predictor. 2

Critical Pitfall in Risk Assessment

• Traditional ASCVD risk calculators consistently underestimate actual cardiovascular risk in HIV patients by 50% or more, particularly in women and Black/African American individuals. 6, 2
• The 2018 ACC/AHA guidelines formally recognize HIV as a "risk-enhancing factor" that should guide cholesterol management decisions. 2

Management Implications

Antiretroviral Therapy Strategy

• Continuous antiretroviral therapy is essential to decrease cardiovascular event risk, as treatment interruption significantly increases myocardial infarction rates. 2
• Newer generation antiretroviral regimens (such as dolutegravir-based therapy) have more favorable lipid profiles and should be preferentially selected. 2
• Consider switching from abacavir-containing regimens in patients with or at high cardiovascular risk due to its association with increased cardiovascular events. 7, 2

Statin Therapy Recommendations

• Based on the REPRIEVE trial, moderate-intensity statin therapy reduced major adverse cardiovascular events by 36% (HR 0.64,95% CI 0.48-0.84) in HIV patients aged 40-75 years with median 10-year ASCVD risk of only 4.5%. 6
• The number needed to treat was 53 or below for those with ≥5% 10-year risk versus 149 or higher for those with <5% risk. 6
• Avoid lovastatin or simvastatin with protease inhibitors due to CYP3A4 interactions that increase rhabdomyolysis risk. 2

Addressing Traditional Risk Factors

• Aggressive management of smoking cessation, hypertension, and diabetes is essential given the amplified risk in HIV patients. 7
• Lifestyle modifications including diet and exercise should be emphasized. 7

Key Clinical Pitfalls to Avoid

• Do not rely solely on traditional risk calculators in HIV patients, as they systematically underestimate actual cardiovascular risk. 2
• Do not delay cardiovascular risk stratification and statin therapy in HIV patients with metabolic syndrome. 7
• Do not use lovastatin or simvastatin with protease inhibitors. 2
• Do not continue abacavir in patients with established or high cardiovascular risk if alternative regimens are available. 7, 2