Men who actually took the pill each day had a far lower risk of getting the AIDS virus. Those reporting taking Truvada at least nine days out of 10 had 73% fewer HIV infections than men taking placebo pills.
The study, dubbed the Pre-exposure Prophylaxis Initiative or iPrEx, began in 2007 in Brazil, Ecuador, Peru, South Africa, Thailand, and the U.S. and included some 2,500 men who have sex with men.
The prevention strategy is called pre-exposure prophylaxis or PrEP. The idea is to give people at extremely high risk of HIV infection a potent but safe and easy-to-take AIDS drug before they get the AIDS virus.
Truvada, a single pill that combines two AIDS drugs, was chosen because it stays in the body for a long time and causes relatively few side effects. Gilead Sciences, which makes Truvada, donated the drug but was not otherwise involved in funding or conducting the study.
HIV experts were quick to hail the findings in a flurry of news releases.
"These results represent a major advance in HIV prevention research," says Kevin Fenton, MD, director of the CDC's division of HIV/AIDS.
"The iPrEx study proves that PrEP provides important additional protection against HIV when offered with other prevention methods such as HIV testing, counseling, condom use, and management of sexually transmitted infections," says study co-chair Robert Grant MD, MPH, of the Gladstone Institute and the University of California, San Francisco.
"iPrEx is a significant advance in HIV prevention," says study co-chair Javier R. Lama, MD, MPH, of Lima, Peru.
"Certainly this is an important finding that provides the basis for further investigating, developing, and employing this prevention strategy, which has the potential to make a significant impact in the fight against HIV/AIDS," says Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which sponsored the study.
"The iPrEx study is a very important addition to what is the most promising 15 months in the field of HIV prevention research since the epidemic began 27 years ago," says Alan Bernstein, MD, executive director of the Global HIV Vaccine Enterprise.
Bernstein notes that the iPrEx findings follow the news that a topical microbicide containing an AIDS drug can cut HIV infections in heterosexual women in Africa by 39% and the suggestion from a Thai trial that it's possible for a vaccine to prevent HIV (although the vaccine tested was itself not sufficiently effective).
PrEP Praise Comes With PrEP Warnings
Unfortunately, it takes more than a daily pill to prevent HIV infection. All of the experts who praised the iPrEx study were quick to warn that it's only one piece in the puzzle.
While the study showed that Truvada can protect gay and bisexual men, it can't be assumed that the same will hold true for heterosexual men and women, for couples in which only one member has HIV, or for intravenous drug users. Studies are under way to evaluate various PrEP formulations in these groups.
Truvada has not been approved by the FDA for prevention of HIV infection.
"It cannot be seen as the first line of defense against HIV," Fenton warns. "PrEP requires careful adherence, and is an intensive approach that won't be right for everyone. … Taking a daily pill is not as simple as it sounds."
In an editorial accompanying the Grant report in the Nov. 23 online edition of the New England Journal of Medicine, Walter Reed Army Institute researcher Nelson L. Michael, MD, PhD, notes the iPrEx study revealed several problems with PrEP:
- Men recently infected with HIV (and thus negative on a standard HIV test) developed drug-resistant HIV infections after starting PrEP.
- A small number of men showed signs of kidney dysfunction, a known side effect of Truvada. This means people taking the drug will have to be closely monitored.
- If so many men failed to take their Truvada every day during the strict confines of a clinical trial, what will happen in the real world?
- What will be the long-term safety of PrEP in people with health issues such as diabetes or high blood pressure?
- Will people taking PrEP forgo condom use, HIV testing, or other measures known to reduce HIV risk?
So what's the next step?
"A variety of expert and community advisory groups at the federal, state, and local levels are looking closely at the study data and will move forward in a deliberative and measured way over the coming months to determine whether and how these findings should be incorporated into ongoing HIV prevention programs," Department of Health and Human Services Assistant Secretary Howard K. Koh, MD, says in a news release.
Meanwhile, the CDC cautions gay and bisexual men and transgendered women that they should still:
- Use condoms consistently and correctly
- Get tested to know their status and that of their partner(s) for certain
- Get tested -- and treated if needed -- for other sexually transmitted infections that can facilitate HIV transmission, such as syphilis and gonorrhea
- Get information and support to reduce drug use and sexual risk behavior
- Reduce their number of sexual partners