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.
Impact of protease inhibitors on lipids
Ritonavir (Norvir) and ritonavir-boosted protease inhibitor combinations cause the most significant increases in lipids. Currently, ritonavir is used in low doses to boost the levels of most other protease inhibitors as the standard of care in protease inhibitor-based regimens. However, in most patients, giving ritonavir with protease inhibitors raises lipid levels, particularly triglycerides.
Most boosted protease inhibitor regimens have similar effects on lipid levels, with some exceptions.
Tipranavir (Aptivus) plus ritonavir, for example, markedly raises total cholesterol and triglyceride levels and would not be recommended for patients with dyslipidemia at baseline.33
Atazanavir (Reyataz)34,35 plus ritonavir and darunavir (Prezista)36 plus ritonavir cause more modest lipid changes. Unboosted atazanavir raises lipid levels only minimally, if at all,34,35 but it is no longer a preferred regimen according to US Department of Health and Human Services guidelines.42
Impact of nonnucleoside reverse transcriptase inhibitors on lipids
Efavirenz (Sustiva), a nonnucleoside reverse transcriptase inhibitor, when added to a regimen of two or three nucleoside reverse transcriptase inhibitors, resulted in modest increases in all lipids, including HDL-C (a potentially beneficial change) at 96 weeks compared with a regimen of three nucleoside reverse transcriptase inhibitors only.43
Nevirapine (Viramune), compared with efavirenz, results in a more favorable lipid profile in previously untreated patients, as shown by larger increases in HDL-C and smaller increases in triglycerides at 48 weeks.44
Etravirine (Intelence), the newest nonnucleoside reverse transcriptase inhibitor, does not appear to cause any further increase in lipids when added to a regimen containing darunavir-ritonavir and nucleoside agents.45
Impact of nucleoside reverse transcriptase inhibitors on lipids
As a class, nucleoside reverse transcriptase inhibitors have been associated with mitochondrial toxicity and insulin resistance,46 but the lipid changes associated with them are generally less significant than those caused by protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Nevertheless, within the class, there is considerable variability in lipid changes associated with specific agents.
Stavudine (Zerit), for example, is associated with hypertriglyceridemia.
Tenofovir (Viread), for another example, in combination with emtricitabine (Emtriva) and the nonnucleoside reverse transcriptase inhibitor efavirenz (the three drugs are contained in a formulation called Atripla) was associated with a smaller increase in fasting total cholesterol than with zidovudine-lamivudine and efavirenz at 96 weeks.47
A recent placebo-controlled, crossover, pilot study of 17 HIV-infected patients suggested that tenofovir may actually have independent lipid-lowering properties.48
Abacavir, as discussed above, has been reported to be associated with a higher risk of myocardial infarction, but this is debatable.
MANAGING CORONARY RISK FACTORS IN HIV-INFECTED PATIENTS
Cardiovascular risk assessment
In HIV patients, cardiovascular risk can be assessed using models derived from large epidemiologic studies such as the Framingham Heart Study.49
Current guidelines from the Infectious Diseases Society of America and the AIDS Clinical Trials Group (ACTG) for evaluating and managing dyslipidemia in HIV-infected adults are based on the National Cholesterol Education Program Adult Treatment Panel III.50 They recommend obtaining a fasting lipid profile before starting antiretroviral therapy and within 3 to 6 months after starting a new regimen.
The guidelines also recommend stratifying risk by counting the number of cardiovascular risk factors, as is done for the general population. If the patient has more than two factors, the Framingham equation should be used to calculate the 10-year risk of myocardial infarction or cardiac death. Interventions should be offered for modifiable cardiovascular risk factors such as smoking, hypertension, physical inactivity, and diabetes mellitus. LDL-C goals should be determined, and lipid-lowering drugs should be initiated accordingly. If triglyceride levels are 200 to 500 mg/dL and levels of “non-HDL-C” (total cholesterol minus the HDL-C level) are high, a statin is recommended. If the triglyceride level is higher than 500 mg/dL, a fibrate should be started.51
