.A Fresh Front in the AIDS War

From Ethiopian refugee camps to East Bay suburbs, a new class of compounds promises success where condom use has failed ­ to stem the spread of HIV.

In 1992, Bethany Young Holt was working in the refugee camps of southern Ethiopia, where thousands of people had fled to escape the civil war in Sudan. She was a master’s student from UC Berkeley’s School of Public Health, there for an internship with the Centers for Disease Control, which was rolling out an HIV prevention program. The camps seemed like an ideal place for it — while very few of the Sudanese refugees were HIV-positive, commercial sex workers from Ethiopian cities were flooding into the camps in search of clients, and their HIV prevalence was 42 percent. It should have been a chance to avert a disaster.

Holt’s job was to teach people to use condoms. “That was just a joke,” she quickly realized. “The women all wanted them and the men wouldn’t put them on for a hundred different reasons.”

Many of these men were really just boys, Holt says. They were part of a culture in which a woman’s social status is tightly linked to childbearing, and where husbands hold absolute authority over their wives. They were stuck in a strange place during hard times, and at least in the very small sphere of their marriages they were still the boss. If they didn’t want to wear condoms, well, that was the way it was.

The Ethiopian sex workers couldn’t convince the men to wear condoms either, and Holt shared their despair. The twin plagues of AIDS and extreme poverty had begotten a generation of young women compelled to do desperate things to survive. Some had become prostitutes to support sick parents or siblings. Others had been kicked out of their families after testing HIV positive. Some had hoped to achieve a better life by doing well in school, but then contracted HIV from their teachers, who demanded sex in return for good grades. One of them, an eighteen-year-old who was fluent in English and yearned to be a doctor, would simply follow Holt around and watch her work. It’s hard to let go of that sort of thing.

And Holt doesn’t let go. A tall woman with shoulder-length blonde hair, fine features, and a sort of gentle, tired smile, she majored in biology in the hope of becoming a vet. Instead, she says, “I fell in love with Africa.” After college she went to Mauritania with the Peace Corps, and then on to a variety of relief agencies including the United Nations’ High Commission for Refugees. By the time she was working in Ethiopia with the CDC, her life’s work had crystallized to a focus on HIV prevention. “It really was sitting in Ethiopia with these girls, who were so well-educated, really sweet girls,” she recalls. “They had babies and mothers and they just had no options, and I realized, gosh, they’re probably going to die.”

It was impossible to ignore the searing irony: The young prostitutes, who existed on the fringe of their society, and the Sudanese wives, who were playing by its strict rules, were equally powerless to protect themselves against disease. The refugee wives, Holt says, “had absolutely no power to negotiate anything in their lives. They couldn’t even go to the clinic in the camp without their husbands’ consent. They would tell us that they knew their husbands were infected with diseases that could hurt them and their babies, but they couldn’t do anything about it. They had been sold by their fathers in Sudan for ten cows, but now those cows were in Sudan and they couldn’t get the cows back. That was their plight.”

It is our plight too. Of the five million people newly infected with HIV every year around the globe, 60 percent are women.

It is significant that a disease many people still think of as primarily afflicting communities such as gay men and intravenous drug users has migrated so easily into the mainstream, into women of childbearing age, particularly women of color, and therefore into every neighborhood and every type of family. On the whole, these women are not engaging in what most people consider risky behaviors. Very often they are married, they are monogamous, they are mothers, and the men they love are the source of their infection.

While it might be comforting to believe that these HIV-positive housewives all live in developing nations, they do not. In California, women have become the fastest-growing population of AIDS patients, and AIDS the leading cause of death for African-American women ages 25 to 34. Most of the women are picking up the virus through heterosexual contact. In fact, when Holt returned from Africa, her next project as a Cal graduate student was to study the health of women in Oakland. “It was amazing to me, the parallel between women in Africa and poor women in our own backyard,” Holt says.

Here again were women in abusive or economically dependent partnerships with little power to negotiate sex or condom use. Here were HIV-positive women infected by long-term male partners. Here were men who refused to use condoms or to take HIV tests for fear of being suspected of being intravenous drug users or of having sex with other men on the down-low.

Holt, currently a lecturer at Cal’s School of Public Health, believed there had to be a better way to protect women. So in the late ’90s, she joined with other public-health experts and researchers who had long envisioned the next best thing to a cure or effective AIDS vaccine: something new to prevent its transmission during sex. Ideally, it would be discreet and female-controlled. It would be cheap enough that clinics in the developing world could give it away, and people in industrialized nations could buy it for about the price of condoms. Most of all, it would have to work.

After twenty uphill years, it is almost here. It’s called a microbicide, a new class of experimental drugs that kill or block HIV on contact. Most are colorless, tasteless, odor-free, and could be applied as lubricating gels, foams, suppositories, or vaginal rings. They’ve been dubbed “invisible condoms” — most likely, a sexual partner wouldn’t even know they’re there. Some can also act as contraceptives; others can kill not only HIV but a broad spectrum of sexually transmitted diseases and common vaginal infections. There are fourteen microbicides now in clinical trials and another fifteen in laboratory development, which employ a range of disease-thwarting strategies (see sidebar “Halting a Killer”). And there is yet another option undergoing preliminary safety tests. If ultimately shown to be effective, it could prove the cheapest, lowest-tech solution imaginable for impoverished women around the world. It literally grows on trees. You probably bit into it the last time you took a tequila shot.

While these anti-HIV prospects have been a long time coming, their potential to slow the global AIDS epidemic could be truly awesome: A mathematical model produced by the London School of Hygiene and Tropical Medicine estimated that if just 20 percent of women in the world’s 73 poorest countries used microbicides half the time, and if those microbicides were only 60 percent effective, it would prevent more than 2.5 million new HIV infections every three years. That’s like sparing the lives of everyone in Alameda and Contra Costa counties.

The catch: None of these drugs has yet been approved by the Food and Drug Administration, and most are years away from retail shelves. Big Pharma, which has the resources to usher them smoothly to market, has pretty much opted out. To be blunt: It is infinitely more lucrative to treat HIV than stop it. What’s more, drug companies are reluctant to invest many millions of dollars developing products for people who have little means to pay for them, and Third World markets in particular.

In truth, microbicides’ potential consumer base is not only far bigger than the drug makers might imagine, but much closer to home.


Liz lives in Oakland. She is a professional in her thirties, with several degrees from prestigious universities. She’s white, heterosexual, and has never used an intravenous drug in her life. She also is HIV-positive. Liz is not her real name, because many of her peers are uncomfortable with the idea that someone like her could have contracted HIV, and through nothing more unusual than unprotected sex with a boyfriend. In fact, there are a lot of women out there just like Liz, and they, microbicide advocates say, are the number one reason American women need — and will buy — this kind of drug.

The most shocking thing about Liz is not how she got HIV, but how thoroughly ill she became before anyone thought to test her for it. When she first began to show symptoms in the late ’90s, she was working as a teacher. She was sick all the time, but chalked that up to working around germy kids. Her hair kept falling out, but she wrote it off as stress. She had chronic yeast infections and abnormal Pap smears, and yet neither her doctor nor her gynecologist suspected anything. “Looking at my face, they didn’t think I was a risk,” she recalls.

She finally took the blood test in 2000, after she’d been hospitalized with a form of pneumonia. Her immune system was in tatters. “I had 18 T-cells — the average person has between 500 and 1,500,” Liz recalls. “If you’ve gone below 200 you automatically have an AIDS diagnosis.” Her viral load was off the charts and, based on her low T-cell count, her doctor estimated she’d been HIV positive three to ten years.

Liz doesn’t know which former boyfriend gave it to her, although she suspects one of two guys with whom she had long-term relationships in her early twenties. At that time, her main concern was avoiding pregnancy, so she faithfully took birth-control pills but was less rigorous about condoms, especially once the relationships grew stable. “It’s hard to be 100 percent adherent to everything,” she says. “Does everyone take their vitamin every day?”

Women are rarely dedicated condom users for all kinds of reasons: to show trust, to make the relationship more intimate, to give the man more pleasure, and simply because it’s easy to take risks in moments of passion. In addition, some cultures both here and abroad encourage early childbearing and stigmatize condom use — this is particularly true among California’s Latinos, many of whom hew to the Catholic teaching that contraception is sinful.

Working with the nonprofit California Microbicides Initiative she cofounded with some other Berkeley grads and now runs, Holt recently conducted a survey of condom use among California women aged eighteen to thirty. The result: Only 17 percent of the women said they always used condoms with steady partners. With casual partners, more women took risks — only 14 percent always used condoms. Holt’s study found that although young women are concerned about preventing pregnancy and STDs, they are less worried about HIV. Public-health educators indeed fear that people who came of age after the ’80s have become blasé about the virus, which seems less scary now that antiretroviral drugs let people live long, relatively healthy lives.

This all adds up to enormous vulnerability for sexually active straight women, particularly because basic anatomical differences make them three to four times more likely than men to pick up HIV through sex.

In Alameda County, 52 percent of known female AIDS cases were acquired through heterosexual contact; in Contra Costa County, that number is 41 percent. But these figures are considered artificially low — they represent only AIDS diagnoses, the final stage of the disease. Clinics have only been obliged to report HIV infections to the government since July 2002. As a result, the data on infection is very thin. And of course, not everyone gets tested — an estimated three-quarters of HIV-positive people don’t yet realize their status.

Although more women are testing HIV-positive, they still face a lonely existence. “Women are more in the closet about their status than gay men,” Liz says, sighing. “The level of acceptance is higher in the gay community. People often say, ‘Why don’t you date a positive guy?’ Well, find me a positive straight guy. It’s called serosorting — in the gay community you can actively seek out and date other positive people, but not in the heterosexual community. They’re more in the closet, women because they’re caretakers and have their families to worry about, and men don’t want to have to worry that people will think they got it from having sex with other men.”

Indeed, part of what allows HIV to fester in a community is its association with so many taboos — infidelity, drug use, gay sex on the down-low, and violence against women. This is one reason Tammy doesn’t know precisely how she got HIV.

Tammy (also a pseudonym) is a lot like Liz, a straight Oakland woman who has never used intravenous drugs. She’s in her mid-twenties, African American, and attending community college in the hope of becoming either a nurse or a mortician. Tammy has been with her boyfriend, the father of her two children, for five years. Like Liz, she relied on hormonal birth control, Depo-Provera in her case, coupled with inconsistent condom use. Like Liz, she may have gotten HIV through unprotected sex with her boyfriend. She also could have been infected during a violent rape she endured while pregnant with her first baby.

Tammy tested positive in 2003, when she was pregnant with her second child. Her boyfriend refused to learn his own status. “He didn’t want to go get tested,” she recalls. “I had snuck him to the doctor’s office and I told him they needed to take his blood for something else.” He also tested positive; they have no way of knowing who was infected first.

In her neighborhood such denial is rampant, Tammy says. She talks privately with other women thanks to groups like Oakland-based WORLD (Women Organized to Respond to Life-Threatening Disease), which provides support and peer counseling for HIV-positive women. Yet nobody talks about their business publicly, she says, and the women have a hard time convincing their men to get tested or use condoms. “You know how they talk — that they like to feel it, they don’t want to use a condom,” she says. “Some of the women just give in.”

Like Liz, Tammy feels isolated. Some friends and family members have turned their backs on her. She’s also waiting anxiously to learn whether her kids have the virus — it takes a few years to tell, but so far both have tested negative. In the meantime, she says, “I just go day to day and live my life and take care of my kids. I’ve had a rough life and now I’m just waking up. I’m just exploring and I’m dealing with it and I’m just trying to reach out and help others.”

Proponents of microbicides tout them as a powerful preventive for women like Liz and Tammy, who neglected to use condoms because they felt relatively safe in a long-term relationship. To encourage consistent use, the drugs could be combined with contraceptives like vaginal rings or diaphragms or packaged as lubricants women can routinely apply before sex. While the first microbicides will be for vaginal use, later ones may also be safe for rectal use. Microbicides that can act as spermicides and protect against other STDs and common infections are expected to further broaden the customer base.

The coming drugs also would benefit those among the estimated 40.3 million HIV-positive people worldwide who wish to protect their HIV-negative partners. For a single person like Liz, they could go a long way toward giving her a more normal love life. “My relationship with my last boyfriend ended in him breaking up with me because of my status. He couldn’t deal with his fear of transmission,” she recalls. “He also did not want to have to use condoms with his girlfriend — he figured it takes away from the spontaneity and the intimacy and he hates them because it doesn’t feel as good, blah blah blah. It really sucked.”

Liz, who knows of microbicides from her HIV-positive peers, says the drugs could still do a lot to protect her, because they can ward off other STDs and additional strains of HIV that might be more resistant to drug therapy. “I’ll be the first one lined up outside to buy it when they open the doors,” she says. “The day when microbicides hit the market will change my life as an HIV-positive woman.”


For women’s-health advocates, 2008 seems so close and yet so far. If all goes extremely well, that’s when the first of this new crop of products will become available. VivaGel — an anti-HIV, anti-herpes microbicide from Australian drug maker Starpharma — was granted FDA fast-track status last month.

Yet most of VivaGel’s peers are only midway through the development pipeline — an optimist would say they’re still three to five years from prime time. Even getting a new drug as far as the FDA is a long haul. It costs about $50 million and takes about a decade to make it through three phases of safety and efficacy trials, the final stages of which require three thousand to ten thousand participants. Kevin Whaley, the head of two biotech companies that are testing microbicides, says this approval process is bound to be even slower than usual since microbicides are an entirely new class of drug.

Big Pharma’s involvement might have sped up drug development considerably, but the industry has its eye on profits, and the new drugs aren’t overnight moneymakers. In a 2002 study, the nonprofit Rockefeller Foundation’s Microbicide Initiative concluded that first-generation microbicides will likely lose money, and companies producing the second generation might break even at best. Those rolling off the line a decade or so from now will probably be profitable, the study said, but only if they’re accepted as a standard hygiene product, like sex lubricants. At its most optimistic, the Rockefeller study envisioned a peak market for the entire class of drugs at $5 billion annually. That’s not too bad, but it’s significantly less than individual blockbuster drugs such as Lipitor, Plavix, and Advair pulled down in 2005.

For that matter, there’s more to be made from HIV treatment than prevention. “The average retail price of one month’s HIV antiretroviral treatment is about $1,500,” says Paula Runnals, training manager for the East Bay AIDS Education and Training Center. “Drug companies make huge amounts of money off of anti-HIV drugs. They’re not going to be making that much money on a product that’s over-the-counter or priced the same as condoms.” Indeed, advocates hope microbicides will end up as cheap, nonprescription items, deeply discounted to Third World distributors — which leaves even less room for blockbuster profits.

Liability issues may also give the big drugmakers pause. Early microbicides will probably be 30 percent to 60 percent effective, although the Rockefeller report estimated that subsequent generations of the drugs will likely reach 80 percent to 97 percent efficacy. If millions of people use these products, even a 30 percent reduction in HIV transmission will save many lives. But drug firms worry about lawsuits, and some wonder whether marketing a preventive drug will lead people to take greater sexual risks. Consider Gilead, a California company that makes anti-HIV treatment Viread. Several public health agencies have been testing the drug as a “pre-exposure prophylaxis” to see if it reduces rates of infection among high-risk people such as sex workers. But the possibility that Viread won’t stop HIV in all cases led Gilead to decide against marketing it for HIV prevention.

Instead, it is small companies like Kevin Whaley’s that are waving the microbicide banner. “We believe there is a very important market in the US for microbicides and we’re very excited about it,” he says. For the first time in his twenty years in the field, Whaley adds, there’s a robust, diverse product pipeline out there.

But further impeding that pipeline are the unique challenges these products face in clinical trials. For one, their ability to block HIV needs to be tested in countries where the virus is highly prevalent. The researchers face obstacles even in California, where companies often test the safety and contraceptive abilities of their new formulations. It can take two to three years just to round up enough women for a contraceptive microbicide trial, notes Ron Frezieres, research director for the Berkeley-based California Family Health Council, which conducts such experiments. That’s because the stakes of being in the placebo group or testing a product that isn’t very effective are high — essentially, the women risk getting pregnant. “If you said, ‘We have a new treatment for heartburn,’ thousands of people would line up that day,” Frezieres says drily. “If you say, ‘We have a new contraceptive,’ you don’t. It’s difficult.”

HIV-transmission trials in foreign countries are even more ethically dicey — nobody wants the placebo group to go without protection. So drug developers provide all study participants with unlimited condoms, teach the women how to use them, and provide free STD screening and treatment — which lowers trial participants’ transmission rates from the outset.

Adding to the glacial pace of development is a dearth of cash. Although government funding has risen in recent years, outlays for global microbicide research totaled just $140 million in 2004. The National Institutes of Health, one of the biggest backers of microbicide work, has ponied up about $66 million to date, yet spends nearly fifty times that on AIDS research every year. Last year, to urge things along, Congress adopted the Microbicides Development Act, which state Senator Jackie Speier then introduced to the California legislature as a resolution to gain the moral support of her colleagues and the attention of California’s booming biotech industry.

Microbicide proponents, meanwhile, find themselves in the weird position of having to raise awareness for a drug no one can buy yet. When AIDS educator Runnals talks to local women about microbicides, she says people get all excited about trying them until she has to admit they won’t be in stores for years. “For a product to get to market there has to be public demand, and before there can be demand there has to be awareness,” she says. “It’s kind of this sick cycle.”

Holt and others have been trying — no luck so far — to get either Oprah or the Vagina Monologues performers to address the gender issues around microbicides. Ideally, Holt would love to see them as a plot point on a show like Grey’s Anatomy or Desperate Housewives.

“Women need to advocate and stand up and shout and make noise for microbicides the way the gay community did in the ’80s for HIV medications,” Runnals urges. “We have all the HIV drugs we do now because the gay community was really active and vocal.”


What if you could get around the excruciatingly long process of having to design and market a new drug?

Anke Hemmerling is a researcher at UC Berkeley’s School of Public Health, and recently, her work took a very unusual twist. Hemmerling is an almost impossibly tall East German, with dark-red hair and alabaster skin — like a cross between Agent Scully from The X-Files and a comic-book superhero. “I spent my whole formative youth behind the Iron Curtain, although that always sounds more dramatic than it actually was,” she says wryly. “I always wanted to do philosophy, which in East Germany wasn’t a possibility. When I finished college I decided to go into medical school — I thought that this is the more practical approach to world revolution.”

Like many East Germans of her generation, Hemmerling traveled the world after the Berlin Wall fell, particularly South America, where she realized she could make the biggest difference as a doctor by going into obstetrics and gynecology. She worked for the nonprofit Salud Sin Límites in the Bolivian Amazon, where she rode a motorcycle from town to town training malaria workers and midwives, and did her hospital rotations in what she calls “obstetrics unplugged” in rural Guatemala. In the late ’90s she returned to Germany and helped convince the government to legalize the abortion pill RU-486 with her dissertation research showing that women who used it fared better psychologically than those who chose a surgical abortion. In 2003, she came to Cal for her master’s, and wrote her thesis on HIV myths in Guatemala.

But more and more, Hemmerling felt torn between the idea of treating individual patients and her desire to develop larger solutions to help thousands of people at a time. “Of course it’s a great thing when we make the difference one at a time, but maybe I’m not patient enough for this one-at-a-time thing,” she muses. “We’re talking about forty million people being infected with HIV — we have to keep this thing in scale.” Her subsequent work has focused on finding low-tech, low-cost preventive measures that might neatly circumvent some of the problems with developing and distributing a new drug. “It’s much more effective and cheaper to prevent infections than treat them later — that’s a no-brainer,” she says.

She was intrigued to learn that many commercial sex workers in northern Nigeria douche with lime juice to prevent infections. Natural microbicides extracted from fruit or other plants could be a particularly elegant way around the pharmaceutical industry. It’s not such a weird idea — for centuries, women have whipped up homemade contraceptives and microbicides from things like lime or lemon juice, vinegar, honey, and olive oil.

With a pH of 2.2, lime juice is sufficiently acidic to kill most microbes, and can neutralize HIV in a test tube in less than a minute. A woman’s body, however, is not a test tube. Was lime juice so acidic, Hemmerling wondered, that it might do more harm than good?

She and other Berkeley researchers decided to put it to the test. At the very least, she figured, they could get the word out if the juice proved dangerous. The microbicide research community, after all, has been cautious ever since a fallout over nonoxynol-9, the ubiquitous spermicide used on condoms and in contraceptive jellies and creams.

Nonoxynol-9 has a good safety record in the United States, and since it kills HIV and some other pathogens in the test tube, some researchers hoped the FDA would also approve it as a microbicide. The thing is, nonoxynol-9 was created for, and primarily used by, people who have sex a few times a week, Hemmerling says. When trials began to test its value as a microbicide among commercial sex workers in Cameroon, who had sex many times a day, a disturbing problem arose. Nonoxynol-9 is a surfactant, which destroys sperm by breaking their outer membranes. But used too often or in high doses, it can damage vaginal tissue, theoretically making it easier for HIV or other pathogens to invade the body. The World Health Organization concluded that nonoxynol-9 has no value as a microbicide. “That really rocked the microbicide community,” Hemmerling says. “After that, everybody went back to square one.” While nonoxynol-9 is still on the market, mostly in low-dose products, only one of the fourteen microbicides in clinical trials is a surfactant.

To test whether frequent exposure to lime juice similarly harms vaginal tissue, Hemmerling’s group recruited Cal students willing to wear tampons soaked in 10 or 20 percent lime juice solutions for two weeks. The results were promising: no one showed serious irritation. On the East Coast, another research team is conducting similar tests with higher juice concentrations — if their results agree, the lowly lime could roll ahead to more extensive safety and efficacy trials.

There may be other natural options — the second-best HIV killer is pomegranate juice — and the active substance in Carraguard, one of the lead pharmaceutical microbicides being tested, is carrageenan, which is derived from seaweed.

Don’t try any of this at home, Hemmerling warns. “It’s a very long road until we can go out there and say this is actually working,” she says. “We don’t want women to read about it and say, ‘This is great, I’m going to start tomorrow,’ and use it and maybe don’t use condoms or whatever other method of protection they are using.” After all, she points out, limes are still just an intriguing possibility, while condoms are definitely highly effective and readily available in America. What’s more, she says, combining lime juice with condoms could compromise the effectiveness of the rubber.

Nevertheless, Hemmerling’s work has given researchers hope that a cheap, readily available alternative is already out there. “Limes grow almost anywhere in the world and are used in a lot of countries in the kitchen,” she points out. For women who need stealth protection, what could be better than one that doesn’t even require a trip to a clinic — one that can be hidden in plain sight?

Indeed, the genius of microbicides is that they put the power in a woman’s hands. Microbicide advocates are sometimes reluctant to use words like “stealthy” to describe the drugs they’re promoting, although they’re well aware that not every woman can discuss her sexual health choices with her partner. But the rising number of HIV infections among women is clearly facilitated by the idea that certain truths — drug use, infidelity, past sexual experiences, HIV status — are unspeakable, even between people who love one another. That silence, and the resulting inability of women to protect themselves against infection, are making them exquisitely vulnerable. With so many secrets working against them, it is well past time for women to have a secret weapon of their own.

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