HIV infected patients who benefit from a new class of drugs that can delay the onset of AIDS may face an increased risk of developing a serious fat-distribution disorder called lipodystrophy.

While not as lethal as AIDS, lipodystrophy--which causes a loss of body fat--as its own serious complications: diabetes and cholesterol disorders. Both increase the risk of heart disease, the No. 1 killer of Americans. A growing number of HIV-positive patients have been diagnosed with lipodystrophy.

The National Institutes of Health has awarded researchers in the Center for Human Nutrition a four-year, 1.8 million grant to study lipodystrophy syndrome in HIV-infected patients. It's the first grant to study the underlying basis and complications of the syndrome.

The World Health Organizations estimated that 30 million people were infected with HIV in 1997. About 40 million are now infected.

Advances in HIV therapy using combinations of anti-retroviral drugs, including protease inhibitors, have dramatically improved the long-term survival of patients with HIV. The lipodystrophy syndrome has been reported in about 65 percent of HIV-infected patients who have taken protease inhibitors for more than a year. Although most reported patients have been men, women may also be affected.

"About two years ago, physicians started reporting that patients taking protease inhibitors for HIV were losing fat in the face and extremities, yet gaining fat in the neck, chin, and truncal areas," said Dr. Abhimanyu Garg, a senior investigator in the Center for Human Nutrition. "While they were experiencing a slower progression of HIV, they were also developing insulin resistance, high triglycerides and glucose intolerance--complications associated with lipodystrophy."

Researchers hope to identify the role protease inhibitors play in causing the syndrome and to understand the mechanisms by which they drugs cause fat redistribution. In addition, they hope to clarify the basis of metabolic complications such as diabetes and high triglycerides. The study may lead to a better definition of the lipodystrophy syndrome and its severity, Dr. Garg said.

"Although protease inhibitors are supposed to be the main culprit here, it is not clear if other HIV drugs, or HIV-infection per se, may be involved. The UT Southwestern study will recruit HIV-infected patients who have never taken protease inhibitors and are relatively healthy. Half will take protease inhibitors; the others will receive equally effective HIV medication. Any study participant who does not experience slowed progression of HIV will be discontinued from the study to pursue HIV treatment.

"I am already seeing in my practice significant impact of lipodystrophy on my patients' quality of life," said co-investigator Dr. Dolores Peterson, associate professor of internal medicine at UT Southwestern. "It is urgent that we learn how to prevent lipodystrophy and lipid abnormalities while also successfully treating HIV disease."

Dr. Garg, professor of internal medicine, has been examining genetic and acquired lipodystrophies for more than a decade and will serve as principal investigator of the study.