The New York Times - July 14, 2004
Lawrence K. Altman

The tests -- some of them under way, others expected to begin by the end of 2004 -- involve more than 28,000 women in the United States, Africa and Asia. A number of other antiviral drugs are being tested in the laboratory or on animals.

A microbicide is at the top of health workers' wish list to protect the many women in poor countries whose husbands refuse to use condoms. A microbicide would also protect an infected woman's sex partners from infection. The need for a microbicide is even more urgent because there is no vaccine for H.I.V.

"Microbicides will not be magic bullets, and microbicides probably will never be as effective as condoms," which are considered nearly 100 percent protective, Dr. Zeda F. Rosenberg, chief executive of the nonprofit International Partnership for Microbicides, said in an interview.

"But even a partially effective microbicide could save millions of lives," she added. Dr. Rosenberg is scheduled to deliver her official report to the conference on Thursday.

It will take 5 to 10 years before any microbicide is marketed, Dr. Rosenberg said, but the drugs may prove more effective in combinations similar to the "drug cocktails" that many infected people now take.

Experience has taught scientists that there is no guarantee of an effective microbicide.

At the AIDS Conference in Durban, South Africa, in 2000, health workers had fully expected that a large trial of a spermicide, nonoxynol-9, would prove effective. But the trial showed that nonoxynol-9 may increase the risk of H.I.V. infection rather than protect against it.

So scientists have shifted their focus to drugs that specifically aim at separate parts of H.I.V.'s life cycle.

An ideal microbicide would work in three ways. First, it would kill H.I.V. in the vagina and cervix. Second, the microbicide would prevent any virus that escapes from attaching to a woman's cells, the way H.I.V. starts to infect. Third, for any virus that does enter cells, the microbicide would block an enzyme, reverse transcriptase, that H.I.V. needs the enzyme to replicate.

At the same time, an effective microbicide would not irritate the vagina or cervix; such damage could enhance the ability of H.I.V. to infect cells.

For example, Dr. Rosenberg said, an ideal microbicide would not kill the bacteria that are normally present in healthy vaginas and that produce hydrogen peroxide, a natural disinfectant. Also, scientists do not want a microbicide to change the acidity of the vagina, allowing unwanted bacteria to flourish.

In developing drugs as microbicides, scientists would need to find ways to deliver them as gels and creams or add them to sponges. Another approach would be to put them in rings that would be inserted into the vagina; the rings would be designed to release the drug over a period of a month or longer.

While cost, stability and ease of manufacturing are critical, "how the product looks, fells, smells, tastes are all critical since a highly effective microbicide that no one likes to use will not prevent any infections," Dr. Rosenberg said.

Australian scientists have conducted limited tests of the acidic juices of lemons and limes that some people have long used as contraceptives in an effort to develop them as microbicides. Dr. Rosenberg said that such juices should go through the same rigorous screening tests that other drugs and chemicals must pass before tests on women can begin.

The classes of drugs being tested include those known as entry inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and membrane active agents.

Viread, a drug made by Gilead Sciences that is prepared as a topical gel, is the only licensed antiviral drug being tested as a microbicide. Viread is a member of the class of drugs known as nucleoside reverse transcriptase inhibitors. The National Institutes of Health is about to begin the second of the three-stage testing system for topical Viread, Dr. Rosenberg said.

Two drugs are in full scale tests as possible microbicides: Savvy, made by Biosyn, which is being tested in Ghana; and Carraguard, which the Population Council is testing in South Africa.

At a cost of from $50 million to $100 million for each trial, $1 billion will be needed to test all candidate drugs as potential microbicides, Dr. Rosenberg said.

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