By David Brown
Washington Post Staff Writer
Wednesday, November 24, 2010; 12:49 AM
When gay men at high risk of becoming infected with HIV through sex take a daily dose of antiretroviral drugs, their chance of catching the virus drops by at least 40 percent, according to a new study.
The protective benefit could be as high as 95 percent if a person is extremely attentive about not missing a dose, the research on nearly 2,500 men on four continents found.
The study provides further proof that the drugs that have transformed AIDS treatment over the past 15 years might be powerful tools in preventing infection, as well. Earlier evidence of that appeared last summer, when a study testing a vaginal gel containing an AIDS drug lowered African women's risk of acquiring HIV by 40 percent.
"This study really represents what I think is a major advance in HIV prevention research," said Kevin Fenton, a physician who directs AIDS prevention activities at the Centers for Disease Control and Prevention, which was not involved in the study. The findings were published Tuesday in the New England Journal of Medicine.
This latest approach adds to a growing menu of strategies for preventing infection in ways other than by urging people to change their behavior. While globally the AIDS epidemic is starting to ebb, gay men remain a risk group in which rates of infection are growing in both rich countries and the developing world. This study offers a new tool to address that problem.
"This is an extremely important advance in our efforts to address HIV in both the United States and globally," said Chris Collins, policy director of the New York-based organization amfAR, the Foundation for AIDS Research.
"This is a great day in the fight against AIDS. It's a result that requires immediate action," said Mitchell Warren, director of AVAC, an AIDS advocacy and educational group.
The researchers running the study warned that its findings apply only to gay men and cannot be extrapolated to men and women at risk of acquiring HIV through heterosexual intercourse.
The use of antiretroviral drugs for prevention is known as "preexposure prophylaxis," or "PrEP" for short. There are about a half-dozen other studies of PrEP strategies underway around the world, testing both pills and gels in heterosexual men and women and IV drug users.
The new findings raise questions that public health authorities are already scrambling to answer.
One is whether it is ethical to use placebos in the other PrEP studies. Another is what to tell doctors and patients who want to start using the strategy now.
The two drugs in the study - emtricitabine and tenofovir - aren't officially approved for AIDS prevention. But doctors can prescribe them for that "off-label" purpose. Sold in combination under the brand name Truvada, they cost $5,000 to $14,000 a year, depending on whether they are bought at retail price or with a bulk discount. In the generic form sold to the poorest countries, however, the combination costs as little as $150 per year.
In the next few weeks, Fenton said, the CDC will provide advice to gay men and their doctors who might want to put the findings into practice immediately. More detailed guidance, as well as cost-benefit calculations that might help determine whether insurance companies will pay for the strategy, will come later.
Fenton and other public health officials are especially worried that gay men might trust the medicines too much.
"It is not time for gay and bisexual men to throw out their condoms or to abandon other ways to prevent HIV," he said.
The director of the study, Robert M. Grant of the University of California at San Francisco, said PrEP should be embarked upon only "under supervision of health-care providers" and needs to be part of an HIV prevention package that includes regular AIDS testing and the delivery of time-honored messages such as the importance of reducing the number of sex partners.
Gay and bisexual men account for nearly half the 1.1 million Americans infected with HIV, and 53 percent of new infections. The infection rate for this risk group has been increasing for more than 15 years.
The study, called the Preexposure Prophylaxis Initiative, enrolled 2,499 men in Peru, Ecuador, Brazil, South Africa, Thailand and the United States. About half were in Peru, and the average age was 27.
As a group, they were at very high risk for acquiring HIV. The average number of sex partners they reported having in the previous three months was 18. Sixty percent reported having unprotected receptive anal intercourse - the riskiest activity - during that time. About 40 percent reported having traded something - food, drink, drugs, shelter or money - for sex.
The subjects were randomly assigned to take the combination of the two antiretroviral drugs, or a look-alike placebo, once a day. They were given extensive prevention counseling, were tested regularly and were given a short course of AIDS drugs if they thought they'd had sex with an infected person - a strategy called post-exposure prophylaxis that's been shown to work.
They were followed for an average of 1.2 years, and during that period 100 became infected with HIV. Thirty-six were in the drug group and 64 in the placebo group. That difference amounted to a 44 percent reduction in the chance of becoming infected in the drug group.
Side effects of the drugs were minimal. About 2 percent of people taking the AIDS drugs experienced nausea or weight loss. About 6 percent of people in both the drug "arm" and the placebo "arm" of the study stopped taking their pills either temporarily or permanently because of side effects.
Although most patients reported taking the pills nearly every day, a count of pills left in their bottles at the end of the month, as well as lab testing of their blood, suggested that many doses were missed. But in those with adequate bloodstream concentration of the drugs, the risk of infection fell 95 percent.
"When people take the drug frequently enough to establish a [target] drug level, they are highly protected," Grant said.
The study cost $44 million. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, provided $28 million, and the Bill and Melinda Gates Foundation provided $16 million. Gilead Sciences, the pharmaceutical company that makes the two drugs, provided them for free but did not otherwise participate in the study.
The new findings come at a time of cautious optimism elsewhere in the effort to prevent HIV infection.
Several studies have shown that circumcision reduces by about 50 percent a man's chance of becoming HIV infected through heterosexual intercourse. There's now a big effort to make the procedure available in AIDS hot spots around the world. The U.S. government, through the President's Emergency Plan for AIDS Relief, or Pepfar, paid for 130,000 circumcisions in 14 African countries last year.
An AIDS vaccine tested in Thailand last year was found to be 30 percent protective, too little for practical use but the first hopeful sign on the vaccine front in years. More recently, molecular studies of HIV-fighting antibodies, and the analysis of the genomes of patients who are able to control HIV infection without drugs, are providing scientists new targets for vaccine development.