Tuesday's announcement that a once-daily pill containing two anti- HIV drugs could reduce the risk of infection by more than 70% in gay men stirred great excitement in the AIDS-prevention world because most previous efforts have failed so abysmally.
"This is a tremendous biomedical, biological success," said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition. "But we are going to have huge challenges in finding out how to translate it into some sort of public health impact."
Dr. Robert M. Grant of the Gladstone Institute of Virology and Immunology at UC San Francisco, who co-chaired the study, has been working in the field since 1983, shortly after AIDS was identified.
"We knew killing the virus was going to be hard, but we thought preventing HIV transmission was going to be easy," he said. "We thought the first vaccine was going to be easy. We thought the first microbicide was going to be effective. We were all very optimistic."
That optimism was not justified because the virus proved much trickier than expected, mutating frequently to evade the best weapons science could throw at it.
To date, there have been 37 completed randomized clinical trials looking at ways to slow the spread of HIV, and almost all have been negative. The only positive trials are three male circumcision trials that showed a mild benefit, a vaccine study last year that showed a small possible benefit, and a study in July that showed that a microbicidal gel used in women could block transmission of the virus by as much as 54% when used faithfully.
"We had to go through a phase where we tried all the easy things," Grant said. "We had to embolden ourselves to consider something like a pill a day, even though it is expensive and requires medical monitoring."
Moreover, antiretroviral drugs that can be given once a day and that are generally well tolerated have been available only in the last 10 years. Truvada, the drug used in the trial, is a combination of tenofovir, approved in 2001, and emtricitabine, approved in 2002. It then took Grant and his colleagues three years to negotiate the final protocol of the study with communities and sponsors, and then a few years more to enroll all the participants.
The trial involved 2,499 gay men and transgender women, groups chosen because they have a high risk of contracting HIV. Gay men account for 53% of all new HIV infections in the United States and a high proportion even in developing countries, so controlling transmission in that group could put a major dent in the epidemic.
"There is a real role for the federal government in taking this study to the next step … a demonstration project in the U.S. and other countries with major HIV epidemics in men having sex with men," said Chris Collins, vice president and director of public policy for amfAR, the Foundation for AIDS Research. "They should take these results and find out how pre-exposure prophylaxis would play out in the real world."
At least half a dozen other studies are underway around the world looking at Truvada and other drugs in more than 100,000 heterosexual men and women and intravenous drug users. Grant is extending the current study to look at long-term effects and is beginning other studies to examine alternative dosing schedules, such as twice a week or before and after sex.
There is no information about effectiveness of the treatment in other groups, but no reason to believe that it will be different than in gay men. "There is no biological reason why it shouldn't work in other groups, but that is not the same as knowing that it does," Grant said.
There have been anecdotal reports that some gay men have been seeking prescriptions for Truvada from their doctors already, but little evidence that that is the case, said Dr. Thomas J. Coates, an infectious diseases specialist at UCLA's David Geffen School of Medicine. "I would expect that to change, but the major impediment is going to be cost."
The drug costs $7,000 to $10,000 per year in the U.S., Coates said, and is not available in generic form. Insurance is not likely to pay for it because prevention is an off-label use now, and most people would not like their medical records to note that they are participating in high-risk sexual activities, he added.