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Genetic Mutation May Make Some More Resistant to AIDS Therapy

High protein levels in blacks speeds expulsion of HIV drugs

Thursday, Aug. 2, 2001 (HealthDayNews) -- A genetic mutation that is common among blacks in America and Africa could mean they have an increased resistance to AIDS drugs, a new study says.

German researchers report that a mutation in the MDR1 gene increases P-glycoprotein, a protein that pumps foreign chemicals out of the body's cells. Unfortunately, this could mean some drug therapies -- including HIV-fighting protease inhibitors -- might not work as well in people of African descent.

The findings appear in the Aug. 4 issue of The Lancet.

Led by Dr. Matthias Schwab, a clinical pharmacologist at the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology in Stuttgart, the researchers looked for the mutation in 800 volunteers, including black Africans, black Americans, white Americans and Japanese people.

Schwab found 83 percent of black Africans and 61 percent of black Americans had the mutation; only 34 percent of the Japanese and 26 percent of the whites had the mutation.

Normally, P-glycoprotein expels chemicals that find their way into cells. Though many drugs are designed to stay inside cells, people with this mutation pump out those chemicals more efficiently.

"You have no therapeutic effect," says Schwab. "The frequency of this MDR1 [mutation] may be important for drug therapy."

The researchers suspect this mutation may evolved to offer an advantage against gastrointestinal tract infections, which are more common in African nations.

Dr. Howard McLeod, an associate professor of oncology at Washington University Medical School, also has studied the prevalence of this mutation in different ethnic groups.

"This validates that there are significant ethnic differences in a DNA change that is now being shown to be important for the function of this protein," says McLeod. "This has implications for HIV protease inhibitors [and] cyclosporin," as well as certain blood pressure and chemotherapy drugs, he says. Cyclosporin is an immunosuppressant commonly used after transplant surgery.

McLeod says whether this particular mutation hurts a person's ability to fight HIV or to have successful transplants still needs to be proven.

Schwab also cautions that the findings rely on DNA evidence from volunteers and laboratory evidence. He says his team does not yet have any data showing that people with this mutation don't respond as well to protease inhibitors.

And it's not clear how drug therapy would have to change, either. Schwab says simply increasing doses of protease inhibitors could lead to more adverse side effects.

Schwab says more must be done to develop new drugs to combat HIV.

McLeod agrees, suggesting the next generation of drugs could be designed to bypass this type of genetic variability.

What To Do

The Centers for Disease Control and Prevention's Division of HIV/AIDS Prevention and the National Institute of Allergy and Infectious Diseases both provide comprehensive information about HIV and AIDS.

Fore more about protease inhibitors, visit the International Association of Physicians in AIDS Care or the HIV/AIDS Treatment Information Service.

SOURCES: Interviews with Matthias Schwab, M.D., clinical pharmacologist and pediatrician, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany, and Howard L. McLeod, M.D., associate professor, Division of Oncology, Department of Internal Medicine, Washington University Medical School, St. Louis, Mo.; August 4, 2001, The Lancet.
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