25 years after HIV discovered, vaccine search goes on

The despair that set in after the failure of the latest effort to develop an AIDS vaccine has given way to a renewed determination on the part of the scientific community, says the Canadian scientist leading an international effort to maximize global activity in the field.

As the world gets ready to mark the 25th anniversary of the publication of the scientific paper announcing the discovery of the virus that causes AIDS, there is a consensus that more, not less, human research is needed in pursuit of the quest, Dr. Alan Bernstein said in an interview Thursday.

Bernstein, who is executive director of the Global HIV Vaccine Enterprise, said he remains hopeful success can be built upon the lessons learned from the failure of the STEP trial and other efforts to date.

"Our genome … is three billion bases [base pairs] of DNA. This virus is about 10 million bases of DNA. We're a lot smarter than this virus," he said.

"So I am an optimist. I think you have to be as a scientist."

"I could not guarantee that one day we'll have a vaccine. But not to try is to say to all the 33 million people who are infected with the virus and the 2.3 million who are becoming infected with the virus every year: 'We're giving up.'"

Virus discovered in Paris in 1983

May 20 marks the 25th anniversary of the publication in the journal Science of a report from Dr. Luc Montagnier and colleagues of La Pitie-Salpetriere Hospital and the Institute Pasteur in Paris that they had discovered what they believed to be the cause of the mysterious and alarming disease known as AIDS.

"A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS)," their historic submission began.

Montagnier and his colleagues named the newly discovered pathogen lymphadenopathy-associated virus or LAV. But it was subsequently renamed the human immunodeficiency virus or HIV.

To mark the anniversary of the publication, Science is publishing an editorial by Bernstein in this week's issue, along with review papers discussing the challenges facing the vaccine effort and a discussion of HIV prevention.

Those who argue the failure of the STEP trial and another, earlier trial are evidence investment in HIV vaccine research is misplaced and the goal cannot be reached "are misguided," wrote Bernstein, who last fall completed a seven-year term as the first president of the Canadian Institutes of Health Research.

"The development of new drugs and new vaccines always takes time and is never a straight line and it's always marked by failures," he explained.

"I think that's sort of just been the history of medicine. What the public hears about, of course, is when there's a success. 'Oh, we have a new vaccine. Fabulous.' But what you tend not to hear about are all the dead ends and false starts and things that go wrong, by and large."

STEP trial shut down

Much hope had been focused on the STEP trial, which tested a vaccine developed by pharmaceutical giant Merck and Co. But last September the study was abruptly halted after it became apparent the vaccine wasn't preventing infection. It was later seen that participants who got the vaccine actually went on to develop HIV at higher rates than those who got a placebo.

The announcement that Bernstein would head the new global enterprise was made a few weeks after the announcement that the STEP trial had been shut down. Rather than feeling deterred by that news, Bernstein said it reaffirmed for him the need to increase the effort.

"When the results came out, I had two reactions actually. One was I was as disappointed as anybody in science about it. And on the other hand, it just reaffirmed for me I had made the right decision to take this job."

In the intervening months, a number of scientific symposiums have been held to try to figure out what went wrong with the Merck vaccine and chart a safe course forward for HIV vaccine development.

What has emerged, Bernstein said, is a consensus that more basic and early-stage clinical research is needed so that science can figure out what happens when a human is infected with the virus.

Such work should also aim at filling in some of the many gaps in understanding about how the human immune system works, he said

That kind of work could also help scientists figure out why asthma rates are rising and how to develop an effective vaccine for malaria, he suggested.

"If we do the kinds of research that's needed to understand how we react to HIV, that ultimately will inform a lot of research on other pathogens."