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Magic Bullet or Menace?

A spray that's supposed to prevent HIV transmission sounds too good to be true.

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On the last Saturday in October around 100 people gathered in a ballroom at the Radisson on East Huron for a $100-a-plate dinner with live jazz. The event was a benefit for the Georgia Doty Health Education Fund, a south-side organization founded by nonprofit executive Don Doty that works in prisons and low-income communities. Representatives from the state and local health departments were there, mayoral and gubernatorial proclamations attesting to the important work being done by the fund were read, and Father George Clements, whom someone called the "black pope," gave an invocation. Then Samuel Evans walked onstage to accept one of the fund's health pioneer of the year awards.

Evans, who lives in Atlanta, made a self-deprecating comment, then talked a bit about himself. He spoke of getting two combat awards in Vietnam, being the first black commander in the Green Berets, and being honored by four American presidents. But, he said, the Doty award was particularly important to him because "a black man singled out another black man." Then he said, "AIDS is going to make the black race extinct if we don't do something," and held up a small rectangular box. Inside was a spray bottle filled with a dark liquid, a product called Genvia that he'd helped develop--the reason for the award. "It will kill HIV, hepatitis, syphilis, and gonorrhea and has the added bonus of killing male sperm instantly to prevent babies from being born with AIDS," he said. "This is history in the making."

Evans explained that his goal was to distribute Genvia in Africa, which has suffered the most from the AIDS epidemic. According to UNAIDS, sub-Saharan Africa is home to 76 percent of the world's HIV-positive women and two-thirds of all HIV-positive people.

But the thought of Genvia being distributed anywhere dismays some of the people who've been involved in the long search for effective microbicides--topical gels and creams or suppositories that would prevent the transmission of HIV. They say there's no proof yet that Genvia is effective and that people using it will think they're protected when they might not be. "Genvia is a huge concern," says Jim Pickett, policy director of the AIDS Foundation of Chicago.

Evans says he was poring over back issues of a newspaper in 1995 when he came across an article that claimed two out of five black females in Washington, D.C., were HIV positive and the ratio was expected to rise to three out of five within seven years. He says he told his wife, who'd just given birth to their daughter, that something had to be done about AIDS and remembers her saying, "You're the guy to do it."

Evans admits he doesn't have the kind of educational background that would make him especially well qualified to tackle the global AIDS crisis. He told me he'd graduated from West Virginia State College with a degree in English and history, though according to the registrar's office he majored in elementary education. He also said he had a law degree from Woodrow Wilson College of Law, though the registrar's office there told me he didn't graduate. He uses the title "Dr." because he has an honorary doctorate from Faith University, whose Web site describes it as a "nonprofit corporation" offering degrees in theology.

His work history also wouldn't appear to make him particularly well qualified to take on the AIDS crisis. He says he's held many jobs--mentioning stints in the oil industry and in investment banking and as a compliance specialist for the U.S. Treasury Department--and never thought of himself as having a profession until he began working full-time to stop the spread of AIDS.

Soon after he saw the newspaper article he met a Chinese pathologist through a friend, and the two got to talking about AIDS. Evans says he presented himself to the doctor as a "simpleminded man with a simple solution." He'd read a research article about how HIV is transmitted and had been struck by the fact that the virus "didn't have great locomotion" in the body before it entered the bloodstream. It seemed obvious to him that "you have to kill the virus before it gets into the bloodstream," and he decided the best way to do that in people having heterosexual sex would be with a "liquid prophylactic" that would coat tears in the vaginal lining caused by the normal friction of sex. The pathologist said it was an "interesting theory," and after he returned to China the two men e-mailed back and forth.

Later that year, says Evans, he agreed to fund a research effort in China "out of pocket" and flew to Nanjing. "The Chinese gave me a wonderful feting," he says. They shuttled him from the airport in a limo, took him to a five-star hotel, and laid out an 18-course meal in his honor. "There were 200 people waiting to have dinner with me," he told the audience at the Doty fund-raiser. "It was just like a movie!"

Evans says that before he went to China he approached pharmaceutical companies in the U.S. and Europe to see if they'd be interested in doing research on an HIV microbicide. "They had no interest in prevention," he says. "There's a great deal of money in treatment." He also says that at the time the idea of a microbicide wasn't being "bandied about."

It's true that pharmaceutical companies didn't have much interest in developing microbicides, and the first major international conference wouldn't be held until 2000. But in the mid-90s plenty of people were talking about and researching microbicides. Women's health advocates in particular understood that there was a need for an alternative to condoms: though condoms are thought to be 80 to 95 percent effective at preventing the transmission of the virus, women don't always have the power or the confidence to insist that their partners use them.

In 1991 health advocates from around the world began meeting with HIV experts to discuss topical treatments to combat the virus, and the following year the U.S. and British governments each began providing a small amount of funding for microbicide research and development.

Around the same time the National Institutes of Health held a conference to discuss possible candidates, including a product already on the market, the spermicide Nonoxyl-9. "Until then women's reproductive health had focused on pregnancy and childbirth," says Anna Forbes, an early advocate for microbicide research who's now deputy director of the Global Campaign for Microbicides. "This was a different biological challenge. One thing that was disconcerting for me as an advocate was that there wasn't much knowledge about how HIV transmission in a vagina occurred. Was it only through breaks in the vaginal lining? Through the cervix? Through the uterus? These were all important questions for the development of microbicides." The NIH wound up funding research on "vaginal ecology" and disease transmission.

In 1993, 11 women's health organizations founded the Women's Health Advocacy Movement to work with the Population Council on developing a microbicide. They helped design an international study to determine what kind of product women would be most likely to use. A gel? A suppository? An applicator? Women needed to be involved "from the get-go," says Forbes. "We said, 'This is too important for you to screw up.'"

Two years later the NIH agreed to pump $1.5 million into microbicide research, and the secretary of Health and Human Services, Donna Shalala, announced a plan to spend another $100 million. By the time Evans went to China, the NIH, FDA, Centers for Disease Control, World Health Organization, UK Medical Research Council, and a host of nongovernmental organizations and research institutes were all working to develop microbicides.

In China, Evans says, "I could feel the friendliness and warmth enveloping me." He says he was also turning over briefcases full of cash, digging into his savings and borrowing against his real estate holdings. "I did whatever it took," he says. His brother chipped in "six figures" (the brother, Tony, says it was over a quarter million). He admits he didn't always know what he was paying for but says he had the utmost faith in the quality of the research. Nanjing, he says, is the "intellectual center for China" with a "tremendous pool of scientists."

He says that a team of researchers, including gynecologists, urologists, and biochemists, went to work on his idea and that by 1998 they'd developed a microbicide spray people could use to coat the vagina or penis before having sex. He also says a series of lab tests determined the spray was "effective in destroying HIV in under 30 seconds."

Anna Forbes says successful lab tests don't mean much: "Soap and water kills HIV in a test tube. It doesn't mean it's capable of killing

it in humans."

But Evans says Genvia was tested further on 100 people at Gulou Hospital in Nanjing for about a year, adding, "I don't absolutely know whether that one year was 10 months or 12 months." He also says that in 2000 he received a certificate from the Chinese Academy of Medicine stating that Genvia had "passed all standards" for use as a "topically applied disinfectant" effective against HIV. He plans to post the test data on a Web site so other researchers can scrutinize it, but the AIDS Foundation's Jim Pickett doesn't understand why Evans has waited six years. "With a valid trial you want that data out there," he says. "You're dying to get it out there."

Evans says the trial was valid

and the quality of the testing was "extremely close" to what would have been done in the U.S. He adds, "Anyone who thinks the tests weren't as thoroughly done is wrong."

The Federal Drug Administration regulates the development of every drug to be sold in the U.S. to ensure that it's safe and effective--and that the risks of using it don't outweigh the benefits. New drugs are tested first in laboratories, then in animals, then in humans. The human trials require three phases of testing, starting with safety tests in small groups. The second phase uses larger groups of people to test safety further and begin looking at effectiveness. The final phase, using even larger groups of people, often over the course of several years, looks at long-term safety and effectiveness.

This long, complicated testing process is made even longer and more complicated in HIV studies by the ethical imperative to educate participants about their risks. Researchers tell participants, who are deliberately chosen from high-risk populations, how the virus is transmitted, provide them with high-quality condoms, and treat any sexually transmitted diseases, which could otherwise increase the chances of contracting HIV. As a result, trial participants often wind up testing HIV positive at a lower rate than the high-risk population they're drawn from.

Four of the microbicides being developed in the U.S. and the UK, which has standards similar to the FDA's, are now in late-stage trials that will last three to four years. Testing is being done largely in Africa and Southeast Asia, in countries where HIV infections are contracted primarily through sex rather than needles. To get meaningful data, the researchers recruited 2,000 to 9,700 participants for each of the trials.

Harold Davis, a consumer safety officer for the FDA, doesn't have any firsthand knowledge of Genvia but says he would have "serious qualms" about any HIV microbicide that was tested on only 100 people, especially in China. According to a recent article in the Lancet medical journal, most HIV-positive people in China contracted the disease from needles used to inject drugs, not from sex.

The FDA regulations are designed in part to uncover bad side effects--a microbicide might, for instance, turn out to cause birth defects or toxic-shock syndrome. They're also designed to determine whether results will vary depending on the dose. Nonoxyl-9 looked promising until phase-three trials among sex workers, when researchers discovered that if used five or six times a day it irritated the vaginal lining so much that the women were more likely to get infected than if they used nothing. "Science only gets partial answers very slowly," says Margaret Scarlett, a former policy analyst for the CDC's HIV, STD, and TB division. "To get a quick fix is not possible with the current technology, as good as it is."

Polly Harrison, director of the Alliance for Microbicide Development, says that's why "the FDA is the gold standard. It's pretty much what people all over the world who want to produce a drug ethically follow." She adds, "It's awkward. It's time consuming. It's expensive. But it's the only safety net we've got." Evans says he's heard similar arguments and dismisses them as stemming from "American arrogance."

More money than ever is now being spent on the effort to find safe and effective microbicides, and not just by the government. Since 1998 the Bill and Melinda Gates Foundation has donated approximately $124 million to groups involved in microbicide research and development--most of it since 2003, when it became clear that half of all new HIV infections occur in women. This past August, at the 16th International AIDS Conference in Toronto, the Gateses gave the keynote address, saying that "stopping AIDS" was their foundation's top priority and calling for the acceleration of microbicide research.

Researchers and advocates are sure safe and effective microbicides will be found, and they're cautiously optimistic about the four being developed in the U.S. and UK. The data won't be in until late 2007 or early 2008, and these first-generation products, all gels, are expected to be only 30 to 50 percent effective. Anna Forbes says a microbicide that's 50 percent effective still can make a significant dent in the spread of HIV, and though the FDA probably wouldn't approve such a product for use in the U.S., the governments of some of the hardest hit countries may be willing to do so until more effective products are developed. Ian McGowan, a professor of medicine at UCLA who helps coordinate NIH-sponsored clinical trials for microbicides, says the hope is that second-generation microbicides will be 50 to 70 percent effective. "Seventy would be great," he says. "I don't think we'd ever anticipate having one be 100 percent effective. Realistically, as scientists we know there aren't many treatments that are 100 percent effective."

When I asked Evans how effective Genvia is he said, "It's either effective or it ain't," adding that in China "it has to be 100 percent effective in human trials or it doesn't get passed." But on the box, he said, "we say it's 99.9 percent effective--because I would prefer that people know there's a risk to any sex."

Evans says that when he heard Genvia had been approved in China in 2000, "I was extremely elated and in a state of disbelief." He estimates that developing a similar product in the U.S. would have cost him $150 million, but Genvia had cost only "several million." When I asked for an exact figure he said, "I'd rather not say."

Without FDA approval, Evans couldn't sell Genvia in the U.S., and in 2001 he approached the agency about getting it. But he says the process would have been "incredibly expensive" and he would have needed more data. He decided to press ahead in other countries. "I want Africa to have it," he says. "I'm not so interested in the commercial aspect. I want to get this disease stopped."

In 2005 Evans founded the Africa AIDS Fund to promote the distribution of Genvia in Africa, and in April of that year the Internal Revenue Service said the fund could operate as a tax-exempt public charity. Evans--who's listed on the fund's Web site as a private investor, an adviser to the board, and CEO of Evans-Carter International, a joint venture with his wife that "specializes in developing health related/

disease preventive products"--says so far he's raised less than $12,000.

At the beginning of the year AAF sent out e-mail touting Genvia. There was a link to the donation page on its Web site, where viewers learned that their tax-deductible gifts would be used to "purchase and distribute drugs to protect people from the virus that causes AIDS." The site states that the fund hopes "to provide Genvia to every person known to be living with AIDS," and it notes that a law has already been passed in Liberia requiring people with HIV and AIDS to use Genvia before having sex (though the product isn't yet available in that country). The site also allows you to download the law, which was passed in February 2005 and states, "The use of Genvia for the prevention of AIDS shall be compulsory, not optional." The Liberian embassy in Washington, D.C., says the document is authentic.

Microbicide advocates worry that advances in the field could be undermined if products whose effectiveness is open to question flood the market. In 2000 the Alliance for Microbicide Development helped stop an American company from selling a vaginal gel overseas that was marketed as the "world's first approved product for preventing AIDS." According to the San Jose Mercury News, the product had never been approved in any country, and the FDA withdrew the company's export certificate for China and several other countries.

"It's important to us, and to the world, that [any] claims be supported by solid research," says the alliance's Polly Harrison. She points out that not only might people think they're protected when they're not, but if a product turns out to be less effective than thought or to have dangerous side effects, it could make potential users skeptical of new microbicides that are safe and effective.

Last January Anna Forbes of the Global Campaign for Microbicides e-mailed Evans at the AAF site asking for more information about Genvia. He wrote back that the Chinese ministry of health had approved it in 2000 "for use against HIV and most sexually transmitted diseases." He added, "While we are starting this concept in Africa, we have a global strategy to use this concept worldwide."

Forbes e-mailed him back, identifying herself as a member of the Global Campaign and asking "where, when, how, and by whom the product was tested" and "what data exist to demonstrate that long-term use of the product is both safe over time (does not damage the vagina in any way that might increase HIV risk) and is effective in preventing or substantially reducing the risk of HIV transmission." She says she didn't get a response.

Last January Evans popped up in an online STD discussion forum after someone posted correspondence with a Chinese doctor who claimed to have invented Genvia. The doctor, Bob Yang, wrote that he'd modified Genvia "because it had certain weaknesses" and created an improved product called Splendo. (Yang didn't respond to an e-mail asking for comment.)

Evans wrote that Yang hadn't invented Genvia but had overseen its development in China. He called Splendo a knockoff, adding, "Dr. Yang dreams of making a 'huge fortune' with this product. My idea was, and is, to use the product to stop the spread of AIDS by giving it to those countries where AIDS is spreading as an epidemic." He went on to say that Genvia could save "millions of women from AIDS" and that it was effective "against most sexually transmitted diseases." When someone asked about buying Genvia, Evans didn't respond.

Anna Forbes wanted to buy some too so she could have it tested, but she couldn't find evidence that it was for sale anywhere in the world. She told a colleague at UNAIDS about Genvia, and soon the World Health Organization's HIV/AIDS team leader in China, Wiwat Rojanapithayakorn, was looking into it.

Rojanapithayakorn says that Genvia was once registered in an eastern Chinese province, Jiangsu, though it was registered for export, not for sale. He says that all such products sold in China must now be registered with the ministry of health, but that Genvia isn't. He also says that its production has been discontinued, and it isn't for sale in China.

Evans insists it's being produced and sold in China, though distribution has been limited to Nanjing. "We're getting ready to do the national rollout," he says. He adds that India has approved Genvia for manufacture in that country once it goes through human trials there. As for Africa, he says that several years ago he donated $320,000 worth of Genvia to various countries, asking that it be given to sex workers, but that it isn't yet for sale on the continent. He says each country has its own process for approving drugs for distribution and that three recently approved Genvia, though he won't say which ones. "Within the next six months you'll see things pick up," he says.

Evans says at some point he'll go through the process to get FDA approval, but not now. "There are 1.3 billion people in China, approximately 1.1 billion people in India, and in the area we're approved in in Africa 350 million," he says. "When you add that up you've got one-third of the world's population. How much approval do you need?"

WHO's Rojanapithayakorn says Genvia is a "form of povidone iodine solution," and Evans acknowledges that it is. Povidone iodine is a common antiseptic most often used in hospitals when preparing skin before surgery, cleansing wounds, and washing hands. According to UCLA's McGowan, it's not a component in any of the products being tested under FDA regulations. "My initial feeling, to be honest, is that I think it would be dangerous," he says. "Mucosa membranes are much more delicate than skin."

Povidone iodine in a lower concentration than that used in hospitals can be bought in drugstores around the world. Walgreens sells an eight-ounce bottle online for $11.99, with the warning "for external use only." Like other povidone iodine products, Genvia is a deep reddish brown, which would make it difficult for women to use without their partner knowing. But Evans says, "She can introduce it into her canal, and there's nothing he can do about it. It's not like a condom--it can't be removed."

Enayat Hakim-Elahi, director of education in the ob-gyn department of the Elmhurst Hospital Center in New York, wrote a letter to the editor of Obstetrics & Gynecology in October 2005 after it published an article recommending that a povidone iodine preparation be used in the vagina before C-sections to decrease the risk of endometriosis. He was worried that the iodine could affect a fetus's thyroid, and the idea of it being used in a microbicide to prevent HIV infections also gives him pause. Iodine, he says, is absorbed by the vaginal wall and alters the biology of the vagina, killing good as well as bad bacteria. "Certain bacteria are necessary for the health of the vagina," he says, adding that too much iodine could affect the functioning of the woman's thyroid or lead to vaginitis, which might increase the risk of infection just as Nonoxyl-9 did.

Evans responds that Chinese gynecologists told him the worst effect of using povidone iodine would be vaginal dryness. "In six years I have not heard a single complaint by users," he says. "Which is worse, the possibility that there may be something that would make the vagina dry or AIDS?"

Art accompanying story in printed newspaper (not available in this archive): photo/Jason Larry.

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