AIDS Study Focuses on 'Elite Controllers'

By David Brown
Washington Post Staff Writer
Thursday, August 17, 2006

TORONTO, Aug. 16 -- Bruce D. Walker thinks there's a chance the key to ending the AIDS pandemic has been hidden in plain view for the past 25 years. He and his collaborators are going to try to find it, using as their guides people he calls "elite controllers."

"It's amazing what you feel when you sit down across the table from one of these people," Walker said Wednesday, his face flushed with excitement. "You just feel the answer is there. You've just got to fish it out."

Elite controllers are people infected with the human immunodeficiency virus (HIV) whose bodies have kept the microbe at undetectable levels in their bloodstreams without treatment. They probably account for about 1 out of 300 people infected with HIV but have been largely invisible to AIDS researchers because they do not get sick, do not qualify for clinical studies and in many cases have very little contact with the health-care system.

Walker, an AIDS researcher at Harvard Medical School, put out a call for these rare patients Wednesday at the 16th International AIDS Conference here. He and his collaborators around the world want to study them in a novel way, scanning their entire genomes to see what unusual mutations, if any, they have in common.

He made his request as other scientists at the 30,000-delegate meeting described finding several substances with HIV-fighting properties that the human immune system makes naturally, but in varying amounts.

Together, the events made it clear that exploring undiscovered corners of the immune system may yet hold extremely important clues for containing the HIV infection in individuals and entire populations.

AIDS researchers have long recognized that a few people infected with HIV live an unusually long time. Scientists have never agreed on a common definition for these "long-term non-progressors," but they are generally people who have healthy immune systems at least 10 years after becoming infected.

Walker wants to study a subset of them -- the ones who have fewer than 50 virus particles per milliliter of blood, a "viral load" undetectable by standard lab machinery. It does not matter how long they have been infected, only that their bodies have achieved that goal without the help of medicines.

Two years ago, Walker said, while giving a lecture to 500 AIDS physicians from around the country, he asked if any had a patient who fit that definition.

"Over half the hands went up. So I thought, 'It has to be true,' " he recalled Wednesday.

The usual tests of immune-system function in previous studies of long-term non-progressors have not found anything they have in common. That was also true of the early studies of elite controllers. In fact, on some tests their response to HIV in lab studies is distinctly sluggish.

Walker and others assume the secret to their ability to suppress the virus that overwhelms most untreated people lies somewhere in the hundreds of genes that direct the immune response. The Human Genome Project identified many of these variations, which are now being mapped at the Broad Institute at the Massachusetts Institute of Technology.

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