International Herald Tribune | July 17, 2008
By Lawrence K. Altman

NEW YORK: Plans for a large human trial of a vaccine against the AIDS virus in the United States were canceled Thursday 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 scientific efforts to develop an HIV vaccine, which health officials contend would be their best weapon to control the AIDS pandemic. A number of other vaccines are in various stages of testing among people in many countries.

But after more than a quarter of a century of trying make an effective HIV vaccine, scientists say that the prospect of marketing the first such prevention is years off, if one is ever developed.

After a meeting sponsored by the National Institute of Allergy and Infectious Diseases last March, many AIDS experts said that researchers must go back to the drawing boards before they could develop an effective HIV vaccine.

The trial canceled on Thursday 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 key U.S. government-funded organizations involved in developing and evaluating experimental HIV vaccines. It aims to develop an effective HIV vaccine that no pharmaceutical company or institution is likely to accomplish on its own.

But the PAVE trial was postponed after another test of a much heralded similar HIV vaccine made by Merck failed in its two main objectives. They were to prevent infection and to lower the amount of HIV in the blood among those who did become infected.

Also, the findings among the 3,000 participants in nine countries in which the Merck vaccine was tested suggested that it might have increased risk among vaccine recipients of becoming infected with HIV.

After a safety-monitoring committee detected the problems with the Merck vaccine last September, the company halted 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 National Institute of Allergy and Infectious Diseases helped pay for the trials of the Merck vaccine.

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 who had pre-existing antibodies to adenovirus type 5.

Following the failure of the Merck trial, the government reduced to 2,400 the number of potential volunteers. 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 Fauci, the director of the institute, said 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 of vaccinated participants who may later become infected with HIV.

At a news conference in 1984, top U.S. government officials said they were optimistic that a marketable HIV vaccine would be available in three years, or 1987.

Since then, AIDS researchers have been divided in their opinion 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 may be a matter concerning the first few days - not weeks - after the virus enters the body, a team headed by Dr. Barton Haynes reported in the Journal of Virology. The findings were based on a study of 30 individuals newly infected with HIV that was paid for by the National Institutes of Health.