Plans for a large human trial of a vaccine against the AIDS virus in the United States were canceled yesterday because federal health officials said the vaccine was unlikely to prove effective and might increase the risk of HIV infection among volunteers.
The decision is another major setback in efforts to develop a vaccine to combat the human immunodeficiency virus, which health officials contend would be their best weapon to control the AIDS pandemic. Several other HIV vaccines are in various stages of human testing in many countries.
Scientists have been trying for more than 25 years to produce an effective HIV vaccine. They say that getting one to market - if one is ever developed - is years away.
After a meeting sponsored by the National Institute of Allergy and Infectious Diseases in March, many AIDS experts said vaccine researchers need to go back to the drawing board.
The trial canceled yesterday was supposed to have begun enrolling 8,500 volunteers last October to receive a vaccine developed by the infectious diseases agency. The study is known as PAVE, for Partnership for AIDS Vaccine Evaluation. PAVE is a consortium of U.S. government agencies and government-financed organizations involved in developing and evaluating experimental HIV vaccines. Its goal is to make an effective vaccine that no drug company or institution is likely to develop on its own.
But the PAVE trial was postponed after a test of a similar vaccine made by Merck failed in its two main objectives: to prevent infection and to lower the levels of HIV in the blood of those who did become infected with the virus that causes AIDS. The findings among the 3,000 participants in nine countries in which the Merck vaccine was tested suggested that it might have increased the risk of becoming infected. After a safety committee detected the problems with the Merck vaccine in September, the company stopped its study immediately.
Scientists have found no obvious explanation for the failure of the Merck vaccine, which had been considered the most promising candidate for an HIV vaccine. The infectious diseases agency helped pay for the vaccine trials.
The Merck vaccine was the first of a new class of HIV vaccines to get to an advanced stage in human testing. The vaccine was made from a weakened version of a common cold virus, adenovirus type 5, which served as a way to deliver three synthetically produced genes from the AIDS virus. Three doses of the vaccine were injected over six months.
Scientific analyses found that the highest risk of HIV infection among recipients of the Merck vaccine were among males who were both circumcised and had pre-existing antibodies to adenovirus type 5.
After the failure of the Merck trial, the government reduced the number of potential volunteers to 2,400. They would include gay men who were circumcised and who had no pre-existing antibodies to adenovirus type 5. The study would have cost about $63 million. Dr. Anthony S. Fauci, director of the infectious diseases agency, now says he would consider a proposal from scientists to conduct a small human trial to focus on only one goal: to determine if the PAVE vaccine significantly lowers the amount of HIV in the blood.
At a news conference in 1984, U.S. officials said they were optimistic that a marketable HIV vaccine would be available in three years. Since then, AIDS researchers have been divided about how fast to test experimental vaccines.
Many urge caution out of fear that failures could destroy confidence among uninfected people most at risk who would be needed as volunteers in future trials.
But equally vocal groups call for testing everything as soon as the research shows promise because of the urgent need for a vaccine.
In an unrelated development, researchers at Duke University reported new findings showing that HIV stuns the immune system earlier than scientists previously understood. The window of opportunity in stopping HIV might be a matter of days - not weeks - after the virus enters the body, a team headed by Dr. Barton Haynes reported in The Journal of Virology.