HIV Drugs May Promote Artery Disease: Mouse Study
February 12, 2003
New research on mice suggests that protease inhibitors may directly contribute to artery disease even before triglyceride and cholesterol levels rise. Dr. Eric J. Smart, the report's lead author, said it is too soon to say whether protease inhibitors have the same effect on people as they did on the mice.Adapted from:
"This doesn't mean that protease inhibitors should be stopped," said Smart, who is at the University of Kentucky Medical School-Lexington. But if the mouse results are confirmed in humans, "we may have to be a little more careful" in how PIs are used. Current screening for triglycerides and cholesterol do not detect the kind of artery problems found in the mouse study, Smart said.
Smart's researchers found that the protease inhibitors ritonavir, indinavir and amprenavir increased levels of the protein CD36 and the enzyme cholesteryl esters in macrophages both in mice and in human cells. The changes are typical of those that occur when lesions build up to clog arteries. Mice given low doses of protease inhibitors developed early artery disease even though their triglycerides and cholesterol levels remained normal.
The study provides the first evidence that protease inhibitors directly affect the development of artery disease, according to Dr. David Y. Hui of the University of Cincinnati College of Medicine, who wrote a commentary on the findings. Hui suggested that protease inhibitors might not only boost levels of triglycerides and cholesterol, but act directly on macrophages. If so, since both actions share a common pathway, it may be possible to develop drugs that would prevent protease inhibitors' artery complications, he noted.
The National Institutes of Health and drug maker Bristol-Myers Squibb funded the study. The report, "HIV Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent of Dyslipidemia by Increasing CD36-Dependent Cholesteryl Ester Accumulation in Macrophages," appeared in Journal of Clinical Investigation (2003;111:317-318;389-397).
02.05.03; Merritt McKinney
This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.