• Risks of Cardiovascular Disease Associated With Highly Active Antiretroviral Therapy Among Persons Treated for HIV/AIDS (Oral 52)
  Authored by A.R. Levy, B. Sobolev, R.S. Hogg, U. Iloeje, J. Mukherjee, B. Yip, M. Harris, M.V. O'Shaughnessy, J.S. Montaner
  

The magnitude of cardiovascular risk associated with antiretroviral treatment has not been well defined. Protease inhibitor (PI)-based therapy has been linked to elevated cholesterol and triglyceride levels. PIs have also been associated with development of insulin resistance and diabetes mellitus. These metabolic changes have been found to contribute to the pathogenesis of atherosclerosis and are independent risk factors for stroke, myocardial infarction and sudden cardiac death. Because of these issues, many physicians and patients are concerned about the future risk of cardiovascular events complicating the course of HIV infection.

In an attempt to see if higher rates of vascular events are developing in patients taking antiretroviral treatment, a number of large cohort studies have been done to track cardiovascular events. Most, but not all, of these cohort studies have shown increased risk of cardiovascular events in HIV-infected patients on antiretroviral therapy.

This new cohort study was presented by an extremely productive group from the British Columbia Centre for Excellence in HIV/AIDS. The purpose of this study was to determine the rate of cardiovascular complications associated with antiretroviral therapy in treatment-naive patients. This ongoing study tracked patients initiating antiretroviral therapy from August 1996 through March 2002. The presentation addressed the overall risk of vascular events in the cohort as well as the impact of choice of antiretroviral therapy on lipids in a substudy.

The lipid substudy was performed with 1,091 patients and changes in lipid levels were tracked after initiation of antiretroviral therapy. There were two significant findings noted in this substudy. First, among patients on PIs there was an 8.3 percent increase in plasma triglycerides per year of exposure. Second, for patients on non-nucleoside reverse transcriptase inhibitors (NNRTIs), (about 80 percent on nevirapine [NVP, Viramune]), there was a 9.3 percent increase in HDL cholesterol per year of exposure. These findings are consistent with previous studies that have demonstrated elevated HDL levels with nevirapine and elevated triglycerides with protease inhibitors.

The entire cohort of 2,937 patients was evaluated for the rate of cardiac events. This included hospitalization for angina, myocardial infarction and cardiac death. One of the strengths of this cohort was the ability of the investigators to access province-wide health care information for British Columbia. They were able to access data regarding the dispensing of antiretroviral medications, complete hospital records and Ministry of Health mortality records. This comprehensive data access lessened the possibility of missing cardiovascular events.

Overall, 2,937 patients were identified that had received at least one month of antiretroviral therapy. After 3.8 total years of follow up there were 28 patients identified with 57 hospital events. Within this cohort, 20 patients had a known history of coronary artery disease and, notably, six of these 20 patients had a cardiac event during follow up.

There were 22 cardiac events counted among the other 2,917 patients in the cohort (0.8 percent). Patients treated with dual nucleoside reverse transcriptase inhibitor (NRTI) therapy were chosen as the referent control group with a relative risk of 1. Patients on NNRTIs were found to have a relative risk of 1.6 (not significant). Patients on PIs were found to have a relative risk of 3.0 (1.0-9.1 for 90 percent confidence limits). These data are consistent with the authors' conclusion that there was a trend for increased risk of cardiac events associated with the use of PIs.

The major weaknesses of this study were the small number of clinical end points and the lack of data on other risk factors for cardiovascular disease.

However, this study does add to the mounting evidence regarding antiretroviral therapy-associated cardiovascular complications. The take-home message from this study is that here is yet another large cohort that has shown an association of protease inhibitor therapy with lipid abnormalities and a trend for increased risk of cardiac events.

The prudent and cautious physician will utilize multiple risk factor assessment to stratify patients into low, medium and high risk categories for cardiovascular disease and will use the National Cholesterol Education Program guidelines. These standards may also be used to guide recommendations regarding lifestyle modification and drug therapy for management of the metabolic complications associated with HIV infection and antiretroviral therapy.