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Novel approach may roust HIV from its hiding places

LOS ANGELES--Disabling a biochemical "pump" that siphons protease inhibitors away from HIV's hiding places in the brain and testes may offer a new way to enhance antiviral therapy for people with AIDS.

The challenge of finding ways to penetrate these sanctuary sites in the body has been critical as scientists try to determine whether HIV ever can be eradicated from the body. In new animal studies, Vanderbilt University researchers led by Edna Choo, PhD, tested a compound called LY-335979 (LY) to see if it blocks the pumping action of P-glycoprotein, which is present in surface cells of blood vessels in the brain and testes. She presented the findings during the annual meeting of the American Society for Clinical Pharmacology and Therapeutics.

Normally, Choo explained, P-glycoprotein "is what pumps out the protease inhibitor from the brain" and other sanctuary sites where HIV escapes attack by the potent antivirals. "It's mechanism is to protect the body from foreign substances by pumping them out," she noted.

Choo's study examined how LY affected penetration by the protease inhibitor nelfinavir in the brain and testes of mice that produce P-glycoprotein, compared with mice that were genetically altered not to produce P-glycoprotein. LY increased the concentration of nelfinavir in brain tissue by 37-fold, and in the testes by 4-fold. At the highest doses given, LY blocked about 75% of P-glycoprotein in the brain and 90% of it in the testes.

P-glycoprotein's role in protecting cancerous tumors from chemotherapy has been studied. But examining its role in making HIV sanctuary sites more accessible to protease inhibitors is a novel approach in attempting to enhance antiviral treatment for AIDS.


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Contact: Kirk Monroe
kmcpr@aol.com
202-789-8101
K-M Communications
14-Mar-2000


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