Newsday - March 28, 2000
Laurie Garrett, Staff correspondent

The need is severe, as newly infected HIV-positive women now well outnumber newly infected men worldwide - largely because they don't have a reasonable way to protect themselves from the risk of infection during intercourse. But for many, there's also little control over when, or even with whom, sexual intercourse occurs. In much of the world, sex is a male-controlled activity.

In recent months momentum has built for development of a vaginal microbicide-a substance that women could use to protect themselves against not only HIV but also other sexually transmitted diseases, such as herpes or gonorrhea. Earlier this month, the first-ever meeting focusing on microbicide development was held in Washington, organized by the National Institutes of Health and the International AIDS Societies.

Such enthusiasm encourages those who hope to slow the global HIV epidemic, but several sizable hurdles must first be overcome. A safe, effective product must be developed. A large pharmaceutical company must agree to manufacture that product. Cultural and political barriers must be pushed aside to allow microbicides into the global marketplace. And, crucially, women and their partners must be willing to use the vaginal gels or foams.

Of all those obstacles, the scientific ones-though considerable- may be the easiest to overcome.

"Today we see a level of seriousness and credibility that microbicide development didn't have before," United Nations AIDS Programme Director Dr. Peter Piot said at the Microbicides 2000 meeting. "It's clear we will have a microbicide before we have an AIDS vaccine if the commitment is real." On a scientific level the commitment to microbicide development does, indeed, seem real.

"We've been ramping up the microbicide program a lot more rapidly than our overall AIDS program," Dr. Neal Nathanson, director of the NIH's Office of AIDS Research, said in an interview. "The situation is so desperate that I think the burden of proof is really on someone who claims we shouldn't pursue every possible avenue of research." This year the NIH will spend some $30 million on basic microbicides research, and National Institute of Allergy and Infectious Diseases director Anthony Fauci has committed his institute alone to a microbicides budget of $27 million next year. The National Women's Health Coalition wants a 2001 NIH microbicide budget of $50 million, and Rep. Nancy Pelosi (D-Calif.) has introduced a bill in Congress that would provide just that. A consortium of American women's health groups, dominated by traditional feminist organizations, has formed the Alliance for Microbicide Development, which hopes to raise $10 million for private research.

The feminist lobbyists cite a telephone survey conducted by the Alan Guttmacher Institute last year as evidence of strong demand for microbicides among U.S. women.

"We determined that 12.6 million women in the U.S. would use microbicides" if such products were available, the Guttmacher Institute's Heather Boonstra told the meeting. Though the group's survey method represented an extrapolation from 1,000 telephone interviews, most attendees to Microbicides 2000 shared a sense that hundreds of millions of women worldwide are ready to buy and use such products.

"I am incredibly enthusiastic," Dr. Sharon Hillier of the University of Pittsburgh said in an interview. "I think there's nothing we're wanting to do with microbicides that isn't doable. There's nothing technical that's insurmountable. This is completely possible." Until very recently scientists felt daunted by the challenge. To obtain U.S. Food and Drug Administration approval, a microbicide would have to effectively block HIV infection of the female genital tract without proving in any way irritable or toxic to the woman or any fetus that she might be carrying.

Ideally, such a product would have to be able to withstand a temperature range from freezing to over 100 degrees Fahrenheit. It would need to be able to function within a vaginal milieu where pH may range from an acidic low of 3.0 to an alkali high of 7.5, even 8.0. It would need to fulfill tough aesthetic requirements to be acceptable for female consumers and their male partners. And it could not kill the natural, beneficial lactobacilli that live normally within the vagina and maintain the environment's health.

"I call these the Xena Warrior Princesses of the vagina," Hillier said of those lactobacilli. "They make little bits of acid and tiny bits of hydrogen peroxide," which, when combined with factors secreted by local human cells, "are a real killer mechanism, very active against HIV," and a host of other infectious agents.

It's a tall order.

In fact, there are several promising agents in the pipeline that meet most of these tough criteria. NIH chemist Brian O'Keefe has been working on one, called cyanovirin-N, or CV-N. It's a compound that seems-in test animals-to completely block HIV entry into cells of the vagina and cervix. CV-N was discovered through an NIH program that pays scientists to collect exotic plants and animals all over the world for analysis as possible cancer and AIDS treatments.

CV-N comes from Hawaiian blue- green algae-pond scum. The algae use the CV-N protein to hook onto one another so that they can float in scum colonies of trillions of connected creatures. Kurt Gustafson of the National Cancer Institute last year isolated CV- N from the algae and discovered that with equal affinity it would latch on to an HIV protein, called gp120. And that protein, it turns out, must poke its way onto a cell for HIV to infect the target; when CV-N is bound to gp120, the virus is rendered harmless.

The large-protein nature of CV-N means it cannot be safely injected or ingested. But it can be mixed into a harmless gel and used vaginally.

It also poses no problem to the "Xena Warrior" lactobacilli, because CV-N exclusively attaches itself to an unusual, complex sugar called oligomannose-9 which, as it turns out, is present exclusively on blue-green algae and the HIV gp120 protein.

And there's an added bonus: CV-N doesn't bind sperm, so women could protect themselves against HIV, but still get pregnant if they wished.

At the Microbicides 2000 meeting, representatives of the NIH patent office posted a large sign reading, "NIH seeks exclusive or non-exclusive licensee(s) to develop and commercialize microbicidal compositions, formulations, devices and/or methods directly incorporating CV-N." Patent office lawyers said they'd had "a few nibbles," but no interest from a pharmaceutical company large enough to scale up CV-N human testing and eventual manufacture.

And therein lies the far more substantial problem inherent in microbicide research: At least a dozen other potential microbicides were presented at the meeting, each of which held promise of fulfilling some or all of the requirements of an HIV microbicide. But only a handful of poorly financed, small biotechnology companies have, to date, shown interest. British consultant Alan Stone surveyed the 30 largest pharmaceutical firms in the world, and 88 percent said that they had no interest in getting involved in microbicide product development. Those who expressed some interest in the products insisted that "someone else," such as government laboratories, must first conduct all necessary safety and efficacy tests.

The major deterrent, from a corporate perspective, is expectations of poor profit returns, economist Michael Reich of the Harvard School of Public Health said, since most of the world's microbicide users would likely be impoverished women.

Further complicating matters are cultural, political and gender- based constraints upon their use in precisely the region of greatest need: Africa.

Flavia Ndikuno, a Ugandan member of the International Community of Women Living With HIV/AIDS, told the meeting that women who use microbicides would be considered "non- obedient" by their mates. And in African societies where men commonly are polygamous, the "non-obedient" wife is rewarded for her behavior with sharp penalties against her children: "The fathers can deprive the children of non-compliant wives," Ndikuno said.

Worse, in much of the region of Africa that is hardest hit by HIV men insist upon so-called "dry sex," Mary Mshana of the Tanzanian Ministry of Health explained. They do not want anything in their partners' vaginas that is lubricating-a feature common to all microbicides currently under research. Any product would, Mshana insisted, have to be a stealth one: It could be there, protecting the woman, but the man must not realize that it is present.

Surveys in England and the United States reveal that 20 to 50 percent of women in those countries share such sentiments, convinced that their male partners would punish them or refuse to have sex if an obvious gel or foam were used.

Nevertheless, said Judy Norsigian, a co-author of the landmark women's health book "Our Bodies, Our Selves," "if there ever was an idea whose time has come, that is the case with microbicides now."

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