In the spring of 2007, it was the next great hope for the fight against AIDS. But by the fall, studies of an experimental vaccine against HIV suggested not only that it did not work, but that it actually put those who received it at greater risk of infection.
Now, AIDS experts are assessing the potential damage of the results of these trials to HIV vaccine research. And while some say the blow is enough to send scientists back to the drawing board, others counter that the findings of the studies are still useful, and research must continue.
At the forefront of the debate is Dr. Robert Gallo, co-discoverer of the human immunodeficiency virus (HIV) and head of the Institute for Human Virology in Baltimore. This week, Gallo told the Washington Post of the failed trial, "This is on the same level of catastrophe as the Challenger disaster," referring to the 1986 explosion of the space shuttle Challenger, which dealt a major blow to NASA's space exploration program.
It is a grim assessment with which some researchers agree.
"At this moment, AIDS vaccine trials are basically dead in the water," said Dr. Gary Simon, director of the Division of Infectious Diseases at George Washington University in Washington, D.C. "Furthermore, who would volunteer given the results?
"The hopes of an AIDS vaccine are dashed."
Dr. Charles van der Horst, professor of medicine at the University of North Carolina at Chapel Hill, concurs. "We need to go back to square one and stop the clinical trials until we have better lab and animal data as how to proceed on the vaccine front," he said.
But others say that though the outcome of the trial was unfortunate, it must not be viewed as a death blow to future HIV vaccine research.
"There is no reason to believe that an HIV vaccine cannot work," said Julia Hurwitz, an HIV researcher at St. Jude Children's Research Hospital in Memphis, Tenn. "There are good vaccine candidates that deserve testing in the HIV field … The field is over-reacting to an hypothesis that has not been proven."
And Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition (AVAC), said the comparison of these trials to the Challenger disaster is inappropriate.
"This type of hyperbole does not help the field," he said. "The trials tell us that one vaccine candidate failed — this is a setback but it is not a catastrophe."
Learning From a Halted Study
The idea behind the vaccine, developed by drugmaker Merck & Co., seemed sound. Developers took a common cold virus, weakened it, and loaded it with three fragments of an HIV virus. The idea was to give the recipient's immune system easy "target practice" against the pieces of the HIV, which alone could not cause the disease.
The trials involved about 3,000 subjects in a total of eight countries: Dominican Republic, Haiti, United States, Australia, Brazil, Canada, Jamaica and Peru. The participants in these trials were mostly gay men and female sex workers who were deemed to be at high risk of contracting the infection, and some received the actual vaccine while others got ineffective "dummy" shots.
But last November, Merck released new details about the research — and the news was not good. In each of the studies, not only did it appear that the vaccine was ineffective at preventing infection with HIV, but the results also suggested that the vaccine increased the risk of infection.
In one of the studies, 49 of 914 men who received the vaccine became infected with HIV, while only 33 of the 922 men who got dummy shots became infected. And in another trial, 24 of 741 volunteers who got the vaccine developed HIV, compared to 21 of 762 participants who got dummy shots.
Questions still linger about why such an effect was seen. Still, the results led Merck to put a halt on the studies on Sept. 21.
At the time, top officials with the company and with the National Institutes of Health, which had partially funded the research, said that the failure of this vaccine did not necessarily spell disaster for similar efforts.
"In my mind, this doesn't damn anything," Dr. Anthony Fauci, head of National Institute of Allergy and Infectious Diseases, told The Associated Press in November. "It tells you you need to be very careful with every aspect [of vaccine design and testing]."
Time to Stop Human Trials?
But now, some AIDS researchers say that the failure of the vaccine should shape the way these vaccines are studied — a potential change that could affect more than a dozen other potential HIV vaccines that are still being investigated.
"If they are already enrolling patients, they should stop enrolling new patients until a review of the underlying science can be done by an independent outside committee of scientists," van der Horst said. "If they have not started enrolling patients, they should not start and an independent committee of scientists should review the science on which the study was based in light of the new data."
But Dr. Michael Keefer, head of the HIV Vaccine Trials Unit at the University of Rochester Medical Center in Rochester, N.Y., said though the information yielded by the studies was disappointing, it is still useful. And he said research must continue.
"We're at a crossroads now," he said. "We're at a time where we know something for certain, and unfortunately only way to know things for certain is to do these studies in people."
And Keefer, for one, said he does not think the Challenger analogy offered by Gallo is entirely inappropriate.
"I think its similar in that it caused a pause in the program for a period of time, which is reasonable to understand exactly what happened and why," he said. "The result of that, though, is they went back to approach they had taken. They are still flying shuttles, anyway."
Audrey Grayson contributed to this report.