News Release

UT Southwestern to study lipodystrophy syndrome in HIV-infected patients

Peer-Reviewed Publication

UT Southwestern Medical Center

DALLAS - September 14, 1999 - A new class of drugs, called protease inhibitors, has successfully delayed the onset of AIDS in people infected with human-immunodeficiency-virus but has been implicated in a fat distribution disorder called lipodystrophy that more and more HIV-positive patients are developing.

While not as lethal as HIV, lipodystrophy - which is a loss of body fat - has its own serious complications: diabetes and cholesterol disorders. Both increase the risk of heart disease, the No. 1 killer of Americans.

The National Institutes of Health has awarded researchers at UT Southwestern Medical Center at Dallas 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 Organization estimated that 30 million people were infected with HIV in 1997. It is expected that 40 million will have it in 2000.

Advances in HIV therapy using combinations of anti-retroviral drugs, including protease inhibitors, have dramatically improved the long-term survival of patients infected 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, professor of internal medicine at UT Southwestern. "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 these 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, 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," Garg said.

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 other 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. "It is urgent that we learn how to prevent lipodystrophy and lipid abnormalities while also successfully treating HIV disease."

Garg, a senior investigator in the Center for Human Nutrition at UT Southwestern, has been examining genetic and acquired lipodystrophies for more than a decade and will serve as principal investigator of the study. Other researchers are Peterson; Dr. Ruth Berggren, assistant professor of internal medicine; Dr. Peter Snell, assistant professor of internal medicine; Dr. Jay Horton, assistant professor of internal medicine; Dr. David Euhus, assistant professor of surgical oncology; Dr. Paul Weatherall, associate professor of radiology; and Dr. Dali Chen, a postdoctoral research fellow in the Center for Human Nutrition. Serving as consultants will be Dr. Richard Koup, chief of infectious disease; Dr. Helen Hobbs, chief of clinical genetics; Dr. Richard Gaynor, chief of molecular virology and chief of hematology/oncology; and Dr. Robert Wolfe of UT Medical Branch at Galveston.

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