Drugs Log

AIDS vaccine researchers are worried about the future of their field after learning an experimental HIV vaccine not only does not work, but just might make recipients more susceptible to infection with the AIDS virus!

They are worried about their volunteers and the future of AIDS vaccines in general. And they are worried because they cannot understand how a vaccine would make a person more vulnerable.

Researchers from Merck & Co., which makes the vaccine, and the National Institute of Allergy and Infectious Diseases, which is helping develop it, said on Wednesday they believe a type of common cold virus used as the basis of the vaccine may somehow have made their volunteers more susceptible to HIV.

They are meeting this week in Seattle to hash through the data and figure out what happened.

This is what they know: Out of 1,500 people vaccinated, 82 became infected with the AIDS virus. Of these, 49 got the vaccine and 33 got a placebo shot.

While they are counseling volunteers that they may have raised their own risk of becoming infected, they are also trying to figure out what happened.

“The data are disappointing and puzzling but we don’t have definitive answers,” Dr. Lawrence Corey of Fred Hutchinson Cancer Research Center in Seattle, who was organizing the trial, told reporters.

Only one woman in the trial became infected with HIV. The rest were men having sex with other men, and it was the men who started out with the highest immune response to the adenovirus 5 common cold bug used to make the vaccine who were the most likely to become infected with the AIDS virus.

But the infected men were also less likely to have been circumcised — circumcision can also prevent HIV infection — and may have engaged in more risky behavior. So did the vaccine actually do something, or were the results a fluke?

“I don’t think we really do know,” Dr. Keith Gottesdiener of Merck Research Laboratories told Reuters.

FUTURE OF THE FIELD

Nearly 30 potential AIDS vaccines are being tested in people around the world.

“It is very important for the future of the field,” said Margaret Johnston, director of the AIDS vaccine research program at the NIAID.

“It makes us rethink some of the candidates that are in trial,” said Dr. Seth Berkley, president of the International AIDS Vaccine Initiative.

Even vaccine advocates are calling it a setback.

“These data are deeply disappointing and troubling, and raise more questions than answers for the field of AIDS vaccine,” said AIDS Vaccine Advocacy Coalition executive director Mitchell Warren.

“This setback should not and can not diminish our commitment to developing an effective HIV vaccine,” said NIAID director Dr. Anthony Fauci. “Every day, another 12,000 people become infected with HIV, most of whom live in resource-poor countries,” he added.

The researchers agree the finding could at the very least scare people off from taking part in AIDS vaccine trials. And because HIV only infects people, having human volunteers is key to finding a way to prevent an infection that has killed 25 million people and affects 40 million more.

“That is why we are being completely transparent, as open as possible,” Fauci said in a recent interview.

Berkley agreed. “I am only worried if there is a lot of buzz, misinformation around,” he said.

But the fact that vaccine volunteers even became infected drives home the need for a vaccine, said Berkley. All the volunteers were counseled about ways to avoid HIV infection, and given condoms. “If those behavioral change interventions worked, we wouldn’t need a vaccine,” Berkley said.

“People will get infected despite the best counseling possible.”

Experimental aids vaccine increased risk

New data on an experimental AIDS vaccine that failed to work shows volunteers who got the shots were far more likely to get infected with the virus through sex or other risky behavior than those who got dummy shots.

The new details, released Wednesday by drugmaker Merck & Co., don’t answer the crucial question of whether failure of the vaccine also spells doom for many similar AIDS vaccines now in testing.

And researchers weren’t sure why more of the vaccinated volunteers wound up getting HIV than those who got dummy shots.

Some 3,000 people, mostly gay men and female sex workers, had volunteered to get the vaccine or dummy shots. All were warned to protect themselves from AIDS exposure.

At the time the study was halted in September, Merck said 24 of 741 volunteers who got the vaccine in one segment of testing later developed HIV; 21 of 762 participants who got dummy shots also were infected.

New data released Wednesday showed that to date, 49 of 914 vaccinated men had become infected with HIV, compared with 33 of the 922 men who got dummy shots.

AIDS vaccine may raise infection risk

More than 3,000 people who volunteered to receive an experimental Merck and Co. AIDS vaccine are being told to come back and get extra tests because the jab may itself raise the risk of infection.

Researchers stress that they do not yet have enough information to say whether those who got the shot indeed are more susceptible to infection with HIV. But they said initial information from the trial, which was stopped suddenly last month, is worrisome.

“At present, there is a tremendous amount of data being analyzed from the … trial to see if there is, in fact, any greater risk of infection in those volunteers who received the vaccine,” Dr. Mark Feinberg, vice president of medical affairs and public health for Merck, said in an e-mail letter.

Two studies were stopped in September after the independent board monitoring one of the trials noticed some troubling data.

“Specifically, 24 cases of HIV infection were seen among the 741 volunteers who received at least one dose of the investigational vaccine, while 21 cases of HIV infection were seen in the 762 participants who received at least one dose of the placebo,” the National Institute of Allergy and Infectious Diseases, which was co-sponsoring the trial with Merck, said in a statement.

This trial, which began in 2004, had enrolled volunteers around the world in the United States, Peru, Brazil, Dominican Republic, Haiti, Jamaica and Australia.

The second trial had begun in South Africa earlier this year, and had enrolled 800 volunteers.

Both Merck and the NIAID say there is no way the vaccine itself could cause infection.

DNA SNIPPETS

The investigational vaccine used in both … studies cannot cause HIV infection because it contains only synthetically produced snippets of viral material. There is no way for these snippets to reconstitute an intact virus,” the NIAID, part of the U.S. National Institutes of Health, said.

“Researchers, however, are analyzing available data to better understand if there may be an increased susceptibility to acquiring HIV infection among those volunteers who received the vaccine.”

The vaccine uses three pieces of DNA from the human immunodeficiency virus that causes AIDS, carried by a common virus that normally causes upper respiratory infections, called an adenovirus.

“Frankly, I think everyone is still trying to figure out what the data means,” said Mitchell Warren of the AIDS Vaccine Advocacy Coalition, who was not involved in either study.

Warren said he hoped the investigation would not frighten people away from taking part in AIDS vaccine trials.

“How people understand this information is going to be critical for this research to continue,” Warren said in a telephone interview.

Close to 40 million people around the world are infected with HIV, which has no cure. The virus has killed 25 million people.

Experts agree that a vaccine would be the best way to fight AIDS but efforts to develop a vaccine have so far been almost completely ineffective. Dozens of potential vaccines are in trials now.