Millions of dollars are being spent to research the feasibility of pre-exposure prophylaxis (PrEP) – the use of AIDS drugs to prevent infection with HIV in the first place. But even if the science proves it to be effective, money, social concerns, and politics may prove to be insurmountable barriers to PrEP ever becoming a significant part of the HIV prevention toolbox.

Those views were apparent during the daylong meeting on PrEP attended by several hundred researchers and community members on August 23, preceding the start of the 2009 National HIV Prevention conference in Atlanta.

Prophylaxis is not a new idea.

"Prevention of mother to child transmission of HIV has been one of the biggest successes in HIV prevention in the last decade," said Connie Celum, a Seattle researcher at the University of Washington. Prophylaxis is used in HIV to prevent opportunistic infections like pneumocystis pneumonia, and more broadly in medicine to protect against exposure to tuberculosis and malaria.

An ideal PrEP drug would be potent, very safe, rapid acting, concentrate in the genital tract, act early in the virus life cycle before it integrates into cellular DNA, have a high barrier to the development of resistance, and be affordable.

Celum said Truvada, a combination of tenofovir and emtricitabine, has these characteristics and has proven to be effective in preventing HIV infection in trials in a small number of monkeys. Human trials currently are under way involving more than 20,000 people throughout the world and the first data on whether or not it works should begin to become available late next year.

Nobody expects it to be 100 percent effective, but then nothing is. Whether it is 30 percent, 50 percent, or 90 percent effective will have a great impact on how likely people are to embrace PrEP.

"There is a high risk for demagoguery about this issue," said Jeff Crowley, director of the Office of National AIDS Policy at the White House. "My nightmare is the cable talk shows saying, this is just another way to let irresponsible homosexuals have more sex."

Crowley also fears that PrEP may lead to greater irresponsible behavior on the part of those who feel they are protected, even though that protection is limited.

"It feels like a lot of people see this as our next magic bullet, and that scares me," he said.

Why PrEP?

Men who have sex with men are the only risk category that has shown an increase in the rate of new HIV infections over the last decade.

It appears that gay men of all backgrounds have come to an accommodation with HIV "and have a reduced sense of concern about it," said Kevin Cranston, director of infectious diseases with the Massachusetts Department of Public Health. It seems to be less and less of a factor in making choices, "so I am looking for different tools to offer," Cranston said.

"PrEP may be our best hope for chipping away at ongoing, extraordinarily high and unacceptable HIV/AIDS rates," particularly among gay men, he added.

Kevin Fenton, of the Centers for Disease Control and Prevention, pointed out that the majority of new infections in gay men are likely to be occurring in stable but serodiscordant partnerships.

"They may well value PrEP as an additional prevention tool that they can use," Fenton said.

Some gay men on the panel said options should be available.

"People think that the penis is this magical thing that you can put a tire around and it is going to function just the way you want it to on demand. That is not necessarily true," said Robert, one of four gay men on a panel who discussed their participation in the PrEP safety trial in Atlanta. "For some people, condoms don't work."

Robert, who was only introduced by his first name, advised that education and counseling will be an important part of getting people to use PrEP properly, often in combination with other prevention options.

Most of the participants in the study were convinced that they were on the placebo because they experienced no side effects from the drugs, said one of the study administrators. Still, they lost many of those who enrolled because participants didn't want to take a pill a day.

In the real world, the people most in need of PrEP will be less motivated and at higher risk for infection than those who spoke on the panel. They will not have the extensive counseling and support that comes from participating in a clinical trial. And while half of new infections occur in those younger than 25, most of the trial participants were older. So, as with virtually all studies, the effectiveness will be lower than what is seen in trials.

Barriers to implementation

Cranston has "significant concerns over whether our medical care system is in any way ready to implement PrEP. ... I'm not convinced that my care providers even have this on their radar screen."

He also fears that euphoria about trials results will bring about a shift of financial resources to PrEP at the expense of existing behavioral and other HIV prevention interventions. He believes those activities already are stretched too thin and that additional new funding will be required to implement PrEP.

Given the financial situation for the federal and state governments, "we are challenged with a question of distributive justice ... how do we go about deciding who will be eligible," Cranston said, to gain access to PrEP through public health programs? Cranston is among those who are concerned that PrEP will reinforce existing racial, ethnic, and geographic disparities in the delivery of HIV services.

"I think it is unconscionable to withhold a potential intervention for people that are HIV negative. ... There is a risk of prioritizing one serostatus over the other," said Craig Washington, a prevention manager with AID Atlanta who works primarily with black gay men.

But others at the meeting argued just as vociferously that it would be unconscionable to pay for expensive drugs for prevention (currently $8,700 a year) when people living with HIV still are not able to access those same drugs for treatment. That is particularly true when the cheap option of condoms are available for prevention but no inexpensive treatment options exist in the U.S.