Lipids (fats) are needed by the body to build cell membranes, make certain hormones, and store energy. Cholesterol and triglycerides are the main types of lipids measured in routine blood chemistry tests. Because lipids do not dissolve in water, they are carried in the blood by special proteins made in the liver. The two main forms of protein-bound cholesterol are called LDL and HDL cholesterol, which are sometimes referred to as "bad" and "good" cholesterol respectively. These terms come from the fact that high LDL levels increase the risk of heart attacks and stroke, while high HDL levels are associated with a decreased risk of these conditions. Measurements of LDL and HDL are usually not a part of routine blood work but may be ordered as part of a special lipid panel. Very high triglycerides can be a concern in the short term because of the risk of pancreatitis (inflammation of the pancreas), and there may be a longer term increased risk of heart attack and stroke associated with high triglycerides.

Many persons on combination therapy are developing abnormally high blood lipid levels, particularly triglycerides. High LDL and low HDL cholesterol levels also seem to be relatively common in patients on protease inhibitors, and may increase the risk of heart attack and stroke. A recent report of two men ages 26 and 37 with high blood lipid levels who developed coronary artery disease while on protease inhibitor therapy highlights the potential risk of lipid elevations.

It is not known if and how protease inhibitors cause lipid elevations. Some researchers have suggested that the drugs act to inhibit the function of human protease enzymes and thereby affect the function of other proteins involved in lipid metabolism. Protease inhibitors are also known to affect the function of liver enzymes called cytochrome P450, which are involved in the metabolism of many compounds. These effects on cytochrome P450 are why many drugs interact with protease inhibitors. Researchers have also theorized that the effects of protease inhibitors on cytochrome P450 may affect the body's metabolism of lipids leading to elevations. Further research is ongoing in an attempt to sort this out.

In the mean time, what should persons taking protease inhibitors do? Many physicians are now testing blood lipid levels on a regular basis (for example, every 3 to 6 months) in their patients on protease inhibitors. These blood tests are optimally done in the fasting state, since food elevates lipid levels, especially triglycerides. Dietary management of elevated lipids may be tried, but many persons ultimately need medication to lower lipid levels. Doctors prescribing cholesterol-lowering drugs must be aware of all of the other medications that the patient is taking because of the potential for drug interactions with protease inhibitors.

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