When the first positive results of a research trial for an antiretroviral-based vaginal microbicide gel were announced at the International AIDS Conference in Vienna this July, it marked a significant thinning of the line between HIV treatment and prevention. The same agents that had been designed and developed to slow the virus's proliferation within the human body  now had the potential to be used to help bar it from successfully setting up shop in the first place.

The findings also suggested that the line between HIV-negative and HIV-positive might soon become much thicker, especially in the developing world, where the virus is mostly spread through heterosexual sex.

"In Africa, one in 10 girls contracts HIV by the time she's 16," notes Yasmin Halima, director for the Global Campaign for Microbicides. "But by the age of 24, one in two will have the virus. This is why these results are so very appealing." 

The promising preventive gel, which cut infection rates among participating women in the South African province of KwaZulu-Natal by 39 percent, contained 1 percent of the antiretroviral (ARV) medication tenofovir, the same drug commonly taken in pill form as part of a standard HIV-treatment regimen. Its apparent safety and success also bodes well for other up-and-coming ARV-based prevention therapies such as pre-exposure prophylaxis (PrEP).

"We need a dramatic increase in the prevention agenda to get down to our goal of 1 to 1.5 million new global infections every year," says Paul De Lay, deputy executive director of the Joint United Nations Program on HIV/AIDS (UNAIDS), adding that the pandemic's annual global growth is currently stabilized at close to 3 million new infections. An estimated 22.4 million people in Sub-Saharan Africa and 3.8 million people in South and Southeast Asia currently live with the virus.

Meanwhile, the money being devoted to AIDS prevention and treatment across the world has also flatlined, forcing careful choices to ensure the "best value for our money," he says. "We can't just treat our way out of the problem. And we can't waste money on interventions that may not be valuable."

The last two decades of strikeouts in microbicide prevention studies could have put this particular strategy into question. In fact, some of the gels tested actually appeared to raise the risk of transmission. But none of these earlier options contained any active ARV drugs.

"It's been a long road, and there have been disappointments," says Halima. "But we now know a lot more about HIV. And we've been able to use that technology not only to develop very effective treatment strategies but also to help reduce the onward transmission of HIV."

"Of course, getting from a p-value in a clinical trial to a microbicide in the hands of a woman is another long journey," she notes.

To translate this breakthrough into something with real public-health impact, researchers need to confirm the findings and address a long list of new questions introduced by them: What is the best dosage and concentration? Could other ARV drugs do better? And what kind of delivery mechanism will best ensure that at-risk women actually use the preventive treatment? Although women in the trial applied the microbicide gel before and after sex, for example, a daily application or long-lasting vaginal ring might fare better.

Optimizing the gel to achieve protection for up to 70 or 80 percent of users would be ideal, notes De Lay. Additional studies will continue for at least the next couple of years. If a product could be rolled out in the developing world by 2013, he suggests it would be an "incredible accomplishment."

Meanwhile, results from ongoing PrEP studies that are evaluating the HIV protection offered by tenofovir alone and in combination with another ARV should become available in a year or two. "If it works as a gel, undoubtedly it will work as an oral drug," predicts De Lay. Subsequent production of the drug for prophylaxis would be expected to happen somewhat faster than for the gel, since it wouldn't need to be newly manufactured.

The idea of using treatment as prevention is not completely new. Keeping HIV viral loads low with early and consistent ARV treatment has a side benefit regarding transmission: people with low HIV viral loads are less likely to infect HIV-negative sexual partners or drug users.

Mother-to-child transmission of HIV has also been significantly reduced with ARVs. "What we're really doing is looking to see if there is a relevant way to adapt that for sexual and blood-borne transmission," says Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition.

The ultimate HIV-prevention strategy might be a combination of tactics, suggests Warren. "We could think about it just like we do reproductive health and family planning," he says. "We have barrier methods such as condoms and diaphragms, oral and injective contraceptives, spermicidal gels and surgical procedures."

The surgical procedure in this case would be male circumcision—another strategy that is starting to get scaled up in the developing world.

"There's never going to be a one-size-fits-all approach," adds Warren. "To achieve prevention for all, we are going to have to be very specific. For some people, PrEP is going to be critical to break the back of the epidemic; for others, it will be the gel."