Gay and bisexual men who took a daily anti-retroviral drug significantly reduced their risk of contracting HIV, according to a study from San Francisco's Gladstone Institutes that public health officials are declaring a major breakthrough in the long struggle to slow down the global AIDS epidemic.

The study, published in today's edition of the New England Journal of Medicine, followed 2,499 men in six countries - including 120 men in San Francisco - with half of them taking the drug Truvada and half taking a placebo. Among the group taking Truvada, which is used to treat people who are HIV-positive, 36 men contracted HIV, compared with 64 men in the placebo group - amounting to a 44 percent reduction in cases.

The drug was meant to be taken daily, but men in both groups often skipped doses. Among men who took the drug at least 90 percent of the time, the group taking Truvada had 78 percent fewer cases of HIV infection.

In other words, when people actually take the drug, it seems to do a very good job of preventing infection, researchers said Monday.

"This is a major advance," said Dr. Robert Grant, a UCSF professor and a researcher with the Gladstone Institute for Virology and Immunology and the lead investigator of the clinical trial. "It will only work if people use it consistently, and the real challenge is how do you use it consistently. Condoms are still our first line of defense, but this could potentially be a very good backup."

Real-world practice

How this study will translate into real-world prevention is the next big question for public health officials, some of whom hailed the study results as the most promising news in HIV/AIDS research in a decade or more.

Several recent studies have revealed some promising new tools toward preventing HIV infection- including circumcision and a gel that, when applied vaginally, offered some protection from infection. And condoms are still the best choice for preventing any sexually transmitted disease.

But with HIV infection still spreading rapidly around the world, and with a vaccine to prevent AIDS proving elusive, public health officials said a drug that appears to be safe and effective is cause for celebration.

"It's an extremely exciting study. The results are very promising," said Dr. Grant Colfax, director of HIV prevention at the San Francisco Department of Public Health. "We need to figure out now if the groundbreaking findings in the study can be used effectively at the community level."

In some developing countries where HIV infections are so widespread that they've become a major burden on the economy and the health care system, a preventive drug would be especially welcome, researchers said. They noted, however, that there could be controversy over whether limited AIDS dollars should go toward prevention or toward treatment of those who are already sick.

Researchers are not recommending that Truvada immediately be used for prevention, and it will probably be at least a year or two before it could be offered widely to people trying to protect themselves.

Local efforts

Public health officials and representatives from Bay Area HIV/AIDS nonprofits will be meeting right away - starting this morning in San Francisco - to discuss how the trial results might affect local prevention efforts.

"Clearly we need to know more about this therapy, and its effectiveness and how to deliver it, but it appears to have great promise," said Dan Van Gorder, executive director of Project Inform in San Francisco. "I think the world is at a real crossroads in terms of its ability to drive this epidemic to an end."

Truvada is a single tablet that combines the drugs emtricitabine and tenofovir disoproxil fumarate. It is made by Gilead Sciences in Foster City and has been used for HIV therapy since 2002.

There are major questions hanging over the study results, researchers and public health officials said. The study looked only at men who have sex with men, and a small number of transgender women, so it would be premature to apply results to women and heterosexual men. All of the study participants were at high risk for contracting HIV.

Cost would be a major concern when considering Truvada for prevention. The drug costs about $750 to $1,000 a month when used to treat HIV infection in the United States, although a generic version is available overseas that costs about 40 cents a day.

Monitoring safety

Drug safety is also something that will need to be monitored closely over time. Side effects from taking Truvada were mostly mild and included headache and nausea, both of which faded after a few weeks, researchers said. Because Truvada has been in use to treat people with HIV infection for almost 10 years, researchers said that at least so far there appear to be no long-term complications from taking the drug, but it's too soon to say for sure.

Perhaps the most critical question for public health officials to consider is adherence. If the drug is to be most effective, people need to take it every day - something that was a struggle in the clinical trial.

Researchers said it is possible that participants didn't feel compelled to take the drug daily because they knew they could be taking a placebo, and they knew that Truvada was untested as a preventive tool. Next year, the study will make Truvada available to all participants, including the placebo group, and researchers hope to find out if people are more likely to take the drug daily if they know more about it.

"This is really just the first exciting step forward," said Dr. Susan Buchbinder, director of HIV research for the San Francisco Department of Public Health. "We are going to be getting more data from this study and other studies that's going to inform how we can expand on this first positive signal.

"We have more than one new infection every day here in San Francisco," she said. "That's a problem that we still have these infections. We need more tools."