Researchers had feared the pills might give a false sense of security and make men less likely to use condoms or to limit their partners, but the opposite happened -- risky sex declined.
The results are "a major advance" that can help curb the epidemic in gay men, said Dr. Kevin Fenton, AIDS prevention chief at the U.S. Centers for Disease Control and Prevention. But he warned they may not apply to people exposed to HIV through male-female sex, drug use or other ways. Studies in those groups are under way now.
"This is a great day in the fight against AIDS ... a major milestone," said a statment from Mitchell Warren, head of the AIDS Vaccine Advocacy Coalition, a nonprofit group that works on HIV prevention.
Because Truvada is already on the market, the CDC is rushing to develop guidelines for doctors using it for HIV prevention, and urged people to wait until those are ready.
"It's not time for gay and bisexual men to throw out their condoms," Fenton said. The pill "should never be seen as a first line of defense against HIV."
As a practical matter, price could limit use. The pills cost from $5,000 to $14,000 a year in the United States, but only 39 cents a day in some poor countries where they are sold in generic form.
Whether insurers or government health programs should pay for them is one of the tough issues to be sorted out, and cost-effectiveness analyses should help, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
"This is an exciting finding," but it "is only one study in one specific study population," so its impact on others is unknown, Fauci said.
His institute sponsored the study with the Bill & Melinda Gates Foundation. Results were reported at a news conference Tuesday and published online by the New England Journal of Medicine.
It is the third AIDS prevention victory in about a year. In September 2009, scientists announced that a vaccine they are now trying to improve had protected one in 3 people from getting HIV in a study in Thailand. In July, research in South Africa showed that a vaginal gel spiked with an AIDS drug could cut nearly in half a woman's chances of getting HIV from an infected partner.
Gay and bisexual men account for nearly half of the more than 1 million Americans living with HIV. Worldwide, more than 40 million people have the virus, and 7,500 new infections occur each day. Unlike in the U.S., only 5 to 10 percent of global cases involve sex between men.
"The condom is still the first line of defense," because it also prevents other sexually spread diseases and unwanted pregnancies, said the study leader, Dr. Robert M. Grant of the Gladstone Institutes, a private foundation affliated with the University of California, San Francisco.
But many men don't or won't use condoms all the time, so researchers have been testing other prevention tools.
AIDS drugs already are used to prevent infection in health care workers accidentally exposed to HIV, and in babies whose pregnant mothers are on the medication. Taking these drugs before exposure to the virus may keep it from taking hold, just as taking malaria pills in advance can prevent that disease when someone is bitten by an infected mosquito.
The strategy showed great promise in monkey studies using tenofovir (brand name Viread) and emtricitabine, or FTC (Emtriva), sold in combination as Truvada by California-based Gilead Sciences Inc.
The company donated Truvada for the study, which involved about 2,500 men at high risk of HIV infection in Peru, Ecuador, Brazil, South Africa, Thailand and the United States (San Francisco and Boston). The foreign sites were chosen because of high rates of HIV infection and diverse populations.
More than 40 percent of participants had taken money for sex at least once. At the start of the study, they had 18 partners on average; that dropped to around 6 by the end.
The men were given either Truvada or dummy pills. All had monthly visits to get HIV testing, more pills and counseling. Every six months, they were tested for other sexually spread diseases and treated as needed.
After a median followup of just over a year, there were 64 HIV infections among the 1,248 men on dummy pills, and only 36 among the 1,251 on Truvada.
Among men who took their pills at least half the time, determined through interviews and pill counts, the risk of infection fell by 50 percent. For those who took pills on 90 percent or more days, risk fell 73 percent. Tests of drug levels in the blood confirmed that more consistent pill-taking gave better protection.
The treatment was safe. Side effects were similar in both groups except for nausea, which was more common in the drug group for the first month but not after that. Unintended weight loss also was more common in the drug group, but it occurred in very few. Further study is needed on possible long-term risks.
All participants will get a chance to take Truvada in an 18-month extension of the study. Researchers want to see whether men will take the pill more faithfully if they know it helps, and whether that provides better protection. About 20,000 people are enrolled in other studies testing Truvada or its component drugs around the world.
The government also will review all ongoing prevention studies, such as those of vaccines or anti-AIDS gels, and consider whether any people currently assigned to get dummy medicines should now get Truvada since it has proved effective in gay men.
Gilead also will discuss with public health and regulatory agencies the possibility and wisdom of seeking approval to market Truvada for prevention. The company has made no decision on that, said Dr. Howard Jaffe, president of Gilead Foundation, the company's philanthropic arm. Doctors can prescribe it for this purpose now if patients are willing to pay for it, and some already do.
Some people have speculated that could expose Gilead to new liability concerns, if someone took the pill and then sued if it did not protect against infection.
"The potential for having an intervention like this that has never been broadly available before raises new questions. It is something we would have to discuss internally and externally," Jaffe said.
Until the CDC's detailed advice is available, the agency said gay and bisexual men should:
--Use condoms consistently and correctly.
--Get tested to know their HIV status and that of their partners, and get tested and treated for syphilis, gonorrhea and other infections that raise the risk of HIV.
--Get counseling to reduce drug use and risky sex.
--Reduce their number of sexual partners.