New clue for HIV drug side effects: study

By Ishani Ganguli

WASHINGTON (Reuters) - Researchers have a new clue about why a widely used AIDS drug has certain side effects such as mysterious fat deposits, they reported on Monday.

Parallels between the side effects of protease inhibitors -- a critical component of HIV drug cocktails -- and genetic conditions that cause early aging may help explain the often debilitating fat deposits and other results, they said.

Protease inhibitors can cause metabolic problems such as an unhealthy buildup of cholesterol in the blood, high blood pressure, and increased risk of diabetes.

They also trigger a condition called lipodystrophy -- a strange redistribution of body fat that gives some patients wasted cheeks and limbs, and a so-called "buffalo hump" of fat on the back of the neck.

Doctors have long been mystified by how protease inhibitors and other HIV drugs cause such effects, which occur in tens of thousands of drug takers worldwide, said Dr. Charles Flexner at Johns Hopkins University School of Medicine, who was not involved in this study.

In an attempt to shed light on this, a group at the University of California Los Angeles and Purdue University in Indiana treated mouse and human cells with protease inhibitor, and found that they accumulated a particularly clumpy form of a protein called prelamin A.

The drug triggered this by blocking the action of another protein -- called ZMPSTE24 -- that converts prelamin A into its useful form, they reported in the Proceedings of the National Academy of Sciences.

Cells with lower levels of ZMPSTE24 to begin with were particularly affected by the protease inhibitor.