Earlier this week, I mentioned the possibility of using drugs taken orally to prevent HIV infection. Dr. Leigh Peterson, of Family Health International reported this morning on the first test of such a drug, tenofovir. Funded by the Gates Foundation, the trial was designed as the first step in what will surely be a long process to determine whether HIV can be stopped with a pill taken before sex or other high risk behavior. While that question won’t be answered for years yet, this first trial does hint that tenofovir is at least safe.

The trial involved over 930 women in Cameroon, Nigeria and Ghana. Half of them were provided with 300 mg of tenofovir, made and donated by Gilead Sciences, every day for a year. The other half were given placebo. Between December 2004 to March 2006, the women came once a month to the study center, where they received their pills as well as pregnancy and HIV tests, pre- and post-HIV infection counseling, and condoms. The women also filled in a detailed sexual behavior questionnaire, and agreed to blood tests to monitor any changes in liver and kidney function (any abnormalities could be signs of adverse effects to the drug). The researchers, however, did not find any significant side effects, and, Peterson noted, “These are really encouraging results regarding safety in this population.”

It’s worth remembering, however, that safety is only the beginning. This trial was noteworthy because the governments of Cameroon and Nigeria withdrew women’s access to the drugs early in 2005, preventing the researchers from collecting enough data to get even a hint of whether the drug might be effective in preventing HIV infection. In Cameroon, the Ministry of Health said it decided to stop the researchers from providing drug because it was concerned about the way the study was designed. In Nigeria, logistical obstacles forced the study to terminate early.

Even so, these results should lay a good foundation for investigating oral prevention drugs further. And there is much more to be done. While taking a pill to prevention infection is certainly a powerful idea, some scientists are already expressing concern about what might happen if such a practice became widespread. Tenofovir is a powerful antiretroviral, and while it was chosen specifically for study as an oral preventive because it’s difficult for HIV to develop resistance to it, there is still the danger that resistant strains of HIV could flourish in an environment where millions of people are taking drugs every day to protect themselves. “I’m worried about oral prevention drugs,” Dr. Martin Markowitz, of the Aaron Diamond AIDS Research Center in New York City told me. “This approach  needs to be done carefully. We already know that monotherapy leads to drug resistance in pregnant women who take a single dose to prevent transmission to their babies. Just think what will happen if people take a drug here and there for a few days. We could be selecting for rapidly resistant strains of HIV.”

That’s why it’s important, as Peterson notes, to include other risk reduction strategies in any study of oral prevention drugs. Peterson provided condoms to all of the women in the study who needed them, and was heartened to find that the percent of women who used condoms during the study actually went up; from 52% who reported using them at their last encounter before the study began, to 94% by the end of the year. While that means that it will be more difficult for the researchers to tease apart exactly how much of the protection came from the drug and how much from the condom, Peterson says it’s a good problem to have; she and her colleagues have no intention of compromising on providing women with the rest of the prevention package, including counseling and condoms. “There are already too many unprotected sex acts in this population,” she says. “We plan to enroll more women, 1,200 women, because the [effectiveness] will be driven by the women who don’t use condoms. So with a larger population, it will be possible to study the drug’s effectiveness.”

Then there are the side effect issues. Remember that the people taking these drugs will be healthy and HIV negative; how much toxicity will they tolerate?

These question will only be answered with more trials, which are already underway. The U.S. Centers for Disease Control is studying tenofovir in Thailand and the U.S. among high risk groups including people who inject drugs and men who have sex with men. The NIH will soon begin a trial in Peru. And thanks to Bill and Melinda Gates, who are making research into oral prevention drugs a priority for their Foundation, more studies will certainly pop up. Stay tuned.

—By Alice Park