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Reducing the Risk of Protease Inhibitor-Related Atherosclerosis

Physiologists may have found a way to decrease the risk of hardening of the arteries that accompanies the long-term use of protease inhibitors//, a class of drugs that has emerged as the most effective treatment against HIV and AIDS.

Writing in the American Journal of Physiology–Cell Physiology, researchers from the University of Kentucky found that when mice were given a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor in combination, it prevented hardening of the arteries often associated with long-term use of protease inhibitors alone. The mice received ritonavir, a common protease inhibitor, in combination with d4T or didanosine, which are common NRTIs.

“The combination prevented the negative cardiovascular effect, hardening of the arteries, of the protease inhibitors without reducing the effectiveness of the protease inhibitors on HIV,” said the study’s senior author, Eric J. Smart. “To our knowledge, these are the first data that indicate that nucleoside reverse transcriptase inhibitors can limit the atherogenic (tendency to form lipid deposits in the arteries) effects of ritonavir,” the authors wrote.

The study also found:
?Although protease inhibitors alone caused cholesterol to build up in mouse arteries, the increased cholesterol could not be detected in the blood. “This means that when doctors test for cholesterol on human patients who are using protease inhibitors, their cholesterol levels may look normal even when they are not,” Smart said. “In other words, the accumulation of cholesterol within the arteries is a silent problem.”

?Although Vitamin E, an antioxidant, has been shown to prevent the negative effects of protease inhibitors in vitro (in the test tube), the vitamin provided no benefit to the mice in this study.

Long-term side effects a concern

Protease inhibitors have been effective in prolonging the lives of people with AIDS, so much so th
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