Coronary heart disease in people infected with HIV
ABSTRACTPeople infected with human immunodeficiency virus (HIV) are living longer thanks to effective antiretroviral therapy. As this population ages, cardiovascular disease is becoming an important cause of morbidity and death. The authors of this review discuss the magnitude and likely mechanisms of the risk and strategies for managing it.
KEY POINTS
- Traditional risk factors are the main contributors to cardiovascular disease in this population, although HIV infection is independently associated with increased cardiovascular risk.
- Antiretroviral therapy contributes modestly to the risk of coronary heart disease. Antiretroviral combinations that include protease inhibitors cause the most substantial deleterious changes in lipid levels.
- Most changes in lipids and insulin resistance can be managed by adding lipid-lowering and antiglycemic agents and may not require changes to the antiretroviral regimen.
- Close attention to drug interactions is important when selecting lipid-lowering medications for patients on antiretroviral therapy to avoid dangerous increases in the levels of certain statins.
- Addressing modifiable risk factors such as smoking, obesity, and sedentary lifestyle can have a far greater impact on cardiovascular risk than changes in antiretroviral therapy.
Dyslipidemia management
In HIV patients, statin and fibrate therapy must be considered cautiously, given the important drug interactions with protease inhibitors and especially ritonavir. Many statins are metabolized by cytochrome P3A4, which protease inhibitors inhibit.
Statins generally considered safe to use with most protease inhibitors:
- Pravastatin (Pravachol)
- Rosuvastatin (Crestor)
- Atorvastatin (Lipitor).
Exceptions and caveats:
- Pravastatin should not be prescribed with boosted darunavir.
- Data for fluvastatin (Lescol) in HIV-infected patients on antiretroviral therapy are limited.
- Lovastatin (Mevacor) and simvastatin (Zocor) are contraindicated with protease inhibitor therapy.52
- In contrast to the increase in statin levels seen with protease inhibitors, efavirenz lowers levels of simvastatin, pravastatin, and atorvastatin.53,54
Ezetimibe (Zetia), which is metabolized independently of the cytochrome P450 system, has been shown to be safe and effective when given to HIV-infected patients on antiretroviral therapy.58
Fenofibrate (Lofibra) is recommended by current guidelines for patients with elevated triglyceride levels (> 500 mg/dL).51 In the ACTG 5087 study, a combination of fenofibrate plus pravastatin was found to be safe and effective in improving lipid profiles.59
Long-acting niacin resulted in significant improvements in triglycerides, total cholesterol, HDL-C, and LDL-C after 48 weeks of use, although insulin sensitivity worsened.60
Fish oil has been shown to be an effective alternative to fibrates, or it can be used in combination with them.61
Switching antiretroviral agents vs adding lipid-lowering agents. In some patients with significant dyslipidemia, switching antiretro viral agents may lower lipid levels without compromising virologic control.62 However, due to the multifactorial nature of dyslipidemia in HIV patients on antiretroviral therapy, switching the HIV therapy alone may not result in sufficient improvement in the lipid profile45 and may be associated with virologic failure, particularly among patients who have underlying treatment-resistant HIV.63
In many cases, adding lipid-lowering agents may be more beneficial than switching the antiretroviral therapy. For example, a randomized trial in HIV-infected patients with hyperlipidemia found that adding a lipid-lowering agent such as pravastatin or bezafibrate to the unchanged antiretroviral regimen resulted in greater improvement in total cholesterol, LDL-C, and triglyceride levels than switching from a protease inhibitor to either nevirapine or efavirenz.64
Given the complexity of prescribing lipid-lowering therapies to patients on antiretroviral therapy, we recommend that providers check with a pharmacist or refer to package inserts and other medical literature if they are unfamiliar with these drug interactions and responses to lipid-lowering therapies.
Managing insulin resistance
Diabetes mellitus is a well-known risk factor for coronary heart disease. The Data Collection on Adverse Events of Anti-HIV Drugs study found a higher incidence of coronary heart disease in HIV-infected patients, with higher rates in those with longer duration of diabetes.65 The prevalence of diabetes in HIV-infected populations varies, depending on demographic characteristics,65,66 prevalence of coinfection with hepatitis C virus,66 and prevalence of exposure to antiretroviral drugs67 in the study population.
Drugs that lessen insulin resistance include the thiazolidinedione rosiglitazone (Avandia) and the biguanide metformin (Glucophage). In a randomized trial, both drugs, alone or in combination, improved insulin sensitivity in HIV-infected patients, but neither lessened the amount of visceral or subcutaneous fat.68
Smoking cessation
Smoking is another well-known modifiable risk factor for coronary heart disease.
The prevalence of smoking is usually higher in HIV patients than in HIV-negative people. For example, a French cohort study reported smoking prevalence rates of 56.6% in HIV-infected men vs 32.7% in HIV-negative men; in women, the rates were 58% vs 28.1%. The 5-year relative risk of coronary heart disease in HIV-infected vs HIV-negative persons was 1.20 for men and 1.59 for women. The estimated attributable risk due to smoking was 65% for men and 29% for women.3
Therefore, smoking cessation should be a top priority in managing cardiovascular risk in HIV-infected patients. In fact, control of modifiable risk factors through lifestyle changes such as smoking cessation, dietary changes, and exercise is likely to have a significant impact on cardiovascular risk in this population.
