San Francisco Chronicle - Tuesday, November 1, 2005
Sabin Russell, Chronicle Medical Writer

Four different compounds under study as AIDS drugs were licensed to the International Partnership for Microbicides of Silver Spring, Md., a nonprofit that is pushing for development of products that would allow women in poor countries to protect themselves from HIV infection by men who will not wear condoms.

"New prevention strategies are definitely needed," said Zeda Rosenberg, chief executive of the partnership. "This is a major milestone in our quest."

The drugs include three experimental AIDS drugs under study by Merck & Co. of Whitehouse Station, N.J., and one by Bristol-Myers Squibb of New York. All four compounds are from a new class of antiviral drugs known as "small molecule entry inhibitors" that would function by preventing HIV, the virus that causes AIDS, from penetrating the immune system cells it typically attacks.

No drug from this class has worked its way through the testing process to become an HIV medicine, so microbicide advocates view the early decision to study their potential for AIDS prevention as a victory for the struggling field.

The goal of developing an effective microbicide has so far proved elusive, but HIV-prevention experts are encouraged that there are now five candidate microbicides in large-scale clinical trials, and several more undergoing studies to determine whether they are safe for bigger tests.

Most are gels or creams inserted into the vagina of an HIV-negative woman. They alter the acidic level in the vagina, creating a hostile environment for viruses, but second-generation microbicides contain drugs that block or kill HIV.

To coincide with Monday's announcement, the British scientific journal Nature released early a study of two of the entry inhibitors showing that they protected macaques from an HIV-like virus up to six hours before sexual intercourse.

Cornell University researcher Dr. John Moore, the lead investigator of the study, noted that much smaller amounts of the drug are provided vaginally as a microbicide than are needed if the same medication is taken orally to treat an infection. Researchers will be monitoring microbicide users for signs that drug-resistant viruses are infecting them, but Moore said drug resistance was much less of a problem when a medicine was used topically to prevent an infection.

Another strategy to boost the effectiveness of medicinal microbicides will be to use them in combination. Dr. Mark Mitchnick, medical director of the International Partnership for Microbicides, said the first microbicide to be tested with these candidate drugs "will be a combination product" using two of the entry inhibitors or one of them in combination with other medicines being explored for microbicide use.

Tenofovir, an AIDS drug sold by Gilead Sciences of Foster City, is already being tested as a microbicide in both India and the United States. The International Partnership for Microbicides is also testing an experimental drug by Johnson & Johnson subsidiary Tibotec.

The Tibotec, Merck and Bristol-Myers Squibb drugs under consideration as microbicides are likely to be slightly different from the medicines under development that will eventually be sold as pills. To work as an oral drug, the chemical compounds must be readily absorbed from the digestive tract into the bloodstream -- a feature not needed in a microbicide. These early versions of the drugs may be modified to make them more suitable for pills, but could be kept in their original form as viable options for microbicides. In a sense, these laboratory castoffs may find a more useful role in preventing AIDS, rather than treating it.

Bristol-Myers Squibb and Merck have agreed to royalty-free licensures of their drugs to the International Partnership for Microbicides, which will use its own money to pay for the research. Its financial backers include the Bill & Melinda Gates Foundation, the Rockefeller Foundation, the U.S. Agency for International Development and the World Bank.

E-mail Sabin Russell at srussell@sfchronicle.com.
051101
SC051101

Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .