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It has now been well established that specific protease inhibitors contribute to hyperlipidemia. One study of ritonavir use in a group of HIV negative controls resulted in an increase in triglycerides, total and LDL-cholesterol levels after just two weeks, without any change in body composition. (7) Another study examined the effect of the protease inhibitor, Indinavir after four weeks in a group of healthy volunteers. Indinavir caused significant endothelial dysfunction independent of drug-induced alterations in blood pressure or lipid profiles. Endothelial dysfunction is highly correlated with coronary artery disease suggesting a potential direct mechanism by which drugs may impact cardiac risk. (8) It is not uncommon for clinicians to observe patients receiving protease inhibitor based regimens with total cholesterol and triglyceride levels above 250 mg/dl and above 500 mg/dl respectively. The development of hyperlipidemia in HIV disease continues to be complicated by patients having abnormally low HDL cholesterol to begin with.
After 1.6 years of follow-up time and four to six years of drug exposure, 126 patients experienced a myocardial infarction in the recent prospective, multinational data collection study on adverse events of anti-HIV drugs (DAD study). (9) The cumulative drug exposure led to a 26 percent increase in the rate of myocardial infarction per year of exposure to antiretroviral drugs with a relative rate of 1.26 (CI: 1.12 to 1.41, p< 0.001). Other factors that were significantly associated with myocardial infarctions were older age, smoking, previous cardiovascular disease, and being male. Hyperlipidemia was identified as a possible explanation for the outcome of myocardial infarctions while the contribution of abnormal body shape changes (fat deposition and/or fat atrophy), diabetes, and hypertension were inconclusive. Although the data suggested a relative increase in rate of myocardial infarctions, the absolute risk was low and must be taken in consideration with the positive benefits of antiretroviral therapy.
