Volume No. 2 Issue No. 15 - Monday October 01, 2007|
Failure of Vaccine Test Is Setback in AIDS Fight
By LAWRENCE K. ALTMAN and ANDREW POLLACK
A much-heralded H.I.V. vaccine has failed to work in a large clinical trial, dealing another serious setback to efforts to stop the AIDS epidemic.
The vaccine’s developer, Merck, said yesterday that it had halted test vaccinations after the vaccine failed to prevent infection or reduce the severity of infection among volunteers who became infected during the trial.
The trial was closely watched because experts considered the vaccine one of most promising to be tested on people so far.
This was also the first of a new class of H.I.V. vaccine to get this far in clinical trials. The failure of the vaccine raises questions about whether the new approach will work.
“This was viewed as the most promising strategy,” said Dr. Mark B. Feinberg, a vice president of Merck, “so I think it is a disappointment for us and a disappointment for everyone in the AIDS vaccine area.”
Dr. Feinberg and others said that the failure reinforced the view that H.I.V. is unlike any infection for which scientists have successfully developed a vaccine.
Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, which conducted the trial with Merck, said in an interview that “the results are obviously disappointing.”
But Dr. Fauci also said it was too soon to draw any broad conclusions about the potential of the new class. Merck said it would share its data with scientists.
Health officials deem development of an H.I.V. vaccine the most important tool they need to control the AIDS pandemic, which rivals the worst in history.
The only H.I.V. vaccine to have undergone full-scale testing was based on the traditional approach of stimulating the immune system to produce antibodies against an infectious agent.
Because that vaccine failed, and similar vaccines also failed in earlier stages of testing, many scientists theorized that AIDS might be controlled by stimulating a different component of the immune system, T cells.
They based their reasoning on the observation that among people infected with H.I.V., those who do well tend to have stronger T-cell responses. So, many scientists held out hope that a vaccine that stimulated a strong T-cell response against H.I.V. in advance would help people stave off an infection.
Experiments on animals and smaller tests on people showed enough promise for Merck to develop and conduct the first large tests of that approach, known as cell-mediated immunity.
The vaccine was made from a weakened version of a common cold virus, which served as a way to deliver three synthetically produced genes from the AIDS virus, known as gag, pol and nef. Three doses of the vaccine were injected over six months.
The trial, which began in late 2004, involved 3,000 uninfected volunteers, largely in the United States and Latin America. The trial was the second of the three-stage system that the Food and Drug Administration typically requires before it licenses any vaccine or drug.
Results of the trial were not expected until the end of 2008 at the earliest. But in its first planned interim analysis of 1,500 volunteers, the board monitoring the trial concluded that it was already obvious the vaccine was not working.
“The results were very clear,” said Dr. Feinberg of Merck.
Among 741 people who received at least one dose of the vaccine, 24 cases of infection were found after volunteers had been followed for about 13 months. That compared with 21 infections out of 762 people who received injections of a dummy vaccine.
Nor did the vaccine reduce the amount of H.I.V. in the blood of those who did get infected, which was a second major goal of the study.
The board advised the investigators, led by Dr. Lawrence Corey of the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, to stop vaccinating volunteers but to continue monitoring them.
Merck is also halting vaccinations in another trial started last year in South Africa.
The latest failure “is in no way the end of the search for an AIDS vaccine,” the AIDS Vaccine Advocacy Coalition said in a statement.
About 30 other H.I.V. vaccines are being tested in people and all work somewhat differently, said Wayne C. Koff, a senior vice president of the International AIDS Vaccine Initiative in New York.
The National Institute of Allergy and Infectious Diseases, for example, plans to test a vaccine based on genes from the AIDS virus followed with a cold-virus vaccine somewhat similar to Merck’s, Dr. Koff said.
In tests on monkeys, this two-step vaccine showed greater effectiveness than the viral-type vaccine alone, he said.