Wall Street Journal - December 4, 2003
Marilyn Chase, Staff Reporter of The Wall Street Journal

The pill, Viread by Gilead Sciences Inc., is already widely used to treat AIDS. But now it is sparking hope that it can act as a shield against HIV, the virus that causes AIDS. In 1995, studies in animals showed that taking the drug prior to HIV exposure prevented the virus from taking hold.

Even before the trials show whether it works, the drug has begun to be used as a morning-after treatment. In cases of accidental HIV exposure, some doctors are prescribing it for 30 days as part of a cocktail of drugs aimed at killing the virus before it proliferates in the body. Recently, the drug has also begun to generate street buzz among men who want to take it as a daily dose of prevention in the event they should become exposed to the AIDS virus.

A preventive is the only real hope of containing the spread of HIV, which already infects 40 million people world-wide. Scientists had hoped a vaccine would fulfill that role, but after years of inconclusive or failed attempts, researchers believe a vaccine is a decade or two away. In the meantime, the Bill and Melinda Gates Foundation and the U.S. government are launching three studies to test Viread (known generically as tenofovir) as a preventive drug among high-risk groups in Africa, Asia and the U.S.

"You can't help but be seduced by the hope. But we do have to nail the data," says Kimberly Page Shafer, an epidemiologist who will fly to Phnom Penh in January to oversee the launch of a University of California study among Cambodian prostitutes in one of the world's highest-risk AIDS zones.

Viread is Gilead's top-selling AIDS drug, expected to bring in $550 million to $570 million in sales this year as a treatment for AIDS. The drug works by blocking a crucial enzyme the virus needs to replicate itself. Scientists also note that it's less toxic than other AIDS drugs and that resistance to it develops at a slower pace. At the recommended treatment doses, the drug costs $4,600 a year wholesale.

Activist physicians who treat AIDS patients in the U.S. and the U.K. were among the prime movers behind the tests of Viread as a prevention drug. Marcus Conant, a veteran AIDS specialist in San Francisco, and Mike Youle, director of HIV clinical research at the Royal Free Hospital in London, began lobbying Gilead, a biotech company based in Foster City, Calif., two years ago. Both doctors prescribe Viread for their patients with AIDS, and they were galvanized by scientific literature suggesting a potential role in prevention.

In addition, Dr. Conant has treated about a dozen men with Viread after accidental sexual exposure to the virus, following condom breakage, for example. He's one of many doctors employing the drug in a regimen known as Post-Exposure Prophylaxis, which combines Viread with older antivirals. In his clinical experience thus far, he says, no patients have been infected with HIV after taking Viread. But he notes that such observations don't provide the hard evidence that the coming clinical trials will provide.

In 1995, scientists from Gilead and the University of California at Davis published studies in the journal Science that showed that a preventive shot of Viread could block a later shot of HIV from infecting monkeys. But it wasn't clear that the drug would block sexual transmission of the virus in people, and Gilead chose to focus on its core mission of getting Viread approved for the treatment of AIDS, which it accomplished in 2001.

In February 2002, as part of the effort to get a study started, Dr. Youle posed a provocative question to software billionaire Bill Gates, who was speaking to AIDS doctors at the Gates Foundation in Seattle. "If I'm having sex with my HIV-positive boyfriend, wouldn't it make sense to take a drug for HIV like you'd take an antimalaria drug?" Dr. Youle asked.

At the time, Mr. Gates voiced uncertainty about using "a drug as a prophylactic," according to people at the meeting. But today, the Gates Foundation has pledged $6.5 million to pay for a randomized, placebo-controlled trial of Viread in 2,000 volunteers in Cambodia, Ghana, Cameroon, Nigeria and, probably, Malawi. For ethical and safety reasons, all study volunteers will also get counseling and condoms even though that may make it harder to determine the impact of the drug.

Plans for other studies have followed. The National Institutes of Health awarded a $2.1 million grant to researchers at the University of California at San Francisco to test Viread in Cambodian women -- mostly prostitutes at risk of acquiring AIDS from their clients. The U.S. Centers for Disease Control and Prevention has granted $3.5 million to fund a third study in Atlanta and San Francisco to weigh Viread's safety in sexually active gay men.

"The race is on," says James Rooney, vice president of clinical research at Gilead, which will supply free drugs for the studies. "Obviously, if the prevention trials are a success, there will be a tremendous number of people who would require" the drug, he says. The company has already begun quietly exploring ways to increase production in case it has a hit on its hands.

Potential risks of the drug include kidney toxicity and bone toxicity, and no one knows how healthy uninfected people will react to taking a daily pill indefinitely. The eventual buildup of resistance is another potential problem.

Along with hope, the drug is also causing concern that a prevention pill could fuel sexual risk-taking and erode condom use. That's especially worrisome in patients currently using it as a preventive agent before it has been shown to work.

"I've heard rumors, stories that people are using it before they go to a sex club or party. There are jokes about packaging it with Viagra," says David Gilden, a former treatment information director of the American Foundation for AIDS Research in New York.

Pre-Exposure Prophylaxis, often called Prep, is a double-edged sword, agrees New York AIDS specialist Howard Grossman. "I know a physician overseas who does his own Prep before he goes to the bathhouse. He's worried about condom breakage."

But Dr. Grossman says he isn't recommending that his patients try this on their own. "I believe in being ahead of the curve," he says. "But if we're wrong, the results could be devastating."

Write to Marilyn Chase at marilyn.chase@wsj.com

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