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Researchers Identify Drug That Might Block Sexual Transmission of HIV - 2004-10-14


Researchers have shown that it may be possible to prevent sexual transmission of the AIDS virus HIV with a compound now in the experimental stage. Female monkeys who received it vaginally were protected from infection by a simian variation of HIV. Such a compound would be helpful to women whose partners are at high risk of the disease.

Many women around the world do not have the power to refuse sex or require their partners to use condoms, so public health officials have been seeking an odorless, tasteless compound a woman could apply privately to block HIV infection.

A new product shown to work in female rhesus monkeys may be what they have been looking for.

Scientists led by Dr. Michael Lederman of Case Western Reserve University in Cleveland coated the vaginal surfaces of 30 monkeys with an experimental drug called PSC-RANTES 15 minutes before exposure to a combined monkey-human virus known as Simian HIV, or SHIV. Dr. Lederman's team reports in the journal Science that, depending on the concentration of the drug, it worked in varying degrees, from complete protection to much less.

"Among the animals treated with the highest dose of PSC-RANTES, none of the animals ever developed virus in their blood, and we confirmed that they weren't infected nor did they actually develop antibodies to the virus in their plasma [blood]," he said.

But Dr. Lederman told a Washington news conference that of five monkeys treated with the lowest dose, only two escaped infection.

PSC-RANTES is a much more potent laboratory version of a protective molecule that occurs naturally in cells on mucous linings such as the vagina and rectum. It was created by Dr. Lederman's co-authors at the University of Geneva. Scientists have known that the natural version of the molecule can block infection by attaching itself to a cell receptor that normally allows HIV to enter. Until now, this receptor was thought to be only one of the cellular doorways through which HIV enters, but the Lederman group has found that it apparently is the most important, for the strengthened PSC-RANTES acting on this receptor alone completely blocked the HIV virus.

In fact, Dr. Lederman says the experimental drug caused the receptor to hide, camouflaging itself from HIV.

"PSC-RANTES binds to the receptor, then receptor goes inside to the cells where it is no longer accessible to the virus," he said.

Dr. Lederman says compounds that prevent HIV from entering the vaginal and rectal linings are urgently needed because the vast majority of infections occur this way. A deputy editor of the journal Science, Katrina Kelner, agrees.

"The identification of an effective anti-viral microbicide drug that can be applied topically to mucous membranes is a high priority for decreasing risk of HIV transmission and interrupting the epidemic," she said. "Dr. Lederman and his colleagues have taken an important step toward that goal."

Dr. Lederman says PSC-RANTES may be ready for testing in women in about one year.

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