AIDS Study Focuses on 'Elite Controllers'

[Guest guest]

AIDS Study Focuses on 'Elite Controllers'

In Unusual Cases, People Are Infected With the Virus but Do Not

Become Ill By Brown, Washington Post Staff Writer

Thursday, August 17, 2006; A08

TORONTO, Aug. 16 -- Bruce D. 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, " 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.

, 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.

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, 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.

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.

An international team that is seeking elite controllers will scan

their genomes for small variations called " single-nucleotide

polymorphisms. " This will cost about $10,000 per subject, said Rafick-

Pierre Sekaly, a researcher at Hospital Saint-Luc in Montreal, where

12 subjects have been identified.

said he has enrolled about 100 through his research group, and

50 have been identified by physicians on the West Coast. Since a

recent newspaper article appeared in the Los Angeles Times, he's been

getting 10 calls a week. Some of the early subjects surfaced through

a mention in Poz, a magazine whose target audience is HIV-positive

people.

That is how Loreen Willenberg, 52, a landscape designer from a town

in Northern California, found out about it. She said that in 1992 she

had a dream that she was infected, went to the health department the

next day and was tested. She was right.

Since then she has been entirely healthy. She enrolled in the elite-

controller project last year, and a week ago she revealed her HIV

status to her friends and neighbors in Diamond Springs.

" I felt that 14 years was long enough to live in the closet, " she

told a news conference Wednesday. " If I've been blessed by this good

health and this unique status, it is my obligation to speak for those

who cannot or will not, " she said.

emphasized that participants in the story do not need to

reveal their status publicly.

Over the next six months, he and his collaborators hope to enroll

1,000 elite controllers and 1,000 " viremic controllers " -- people who

have kept their viral load between 50 and 2,000 viruses per

milliliter.

That second group is considered important because people taking AIDS

drugs who are able to keep their viral load below 2,000 have a very

low rate of disease progression and of infecting others through

sexual activity.

A vaccine that kept the infection that much in check would be highly

useful. It would keep people well and would lead to few new

infections. It would be " a recipe for the contraction of the

epidemic, " said.

The problem is that researchers do not know how such a vaccine would

need to stimulate the immune system.

" What are we aiming for? Well, nobody really knows. But there is a

reasonable chance that we will come up with something with this

effort, " he said.

Other researchers here talked about other emerging insights into

natural resistance to HIV infection.

Shehzad Iqbal, a graduate student at the University of Manitoba, said

he and his collaborators had found a substance called trappin-2 in

the vaginal fluid of a small number of prostitutes in Nairobi, Kenya,

who have not been infected by HIV despite hundreds of exposures.

The women have been the subjects of close study by a team of Canadian

researchers since they were identified in 1984. What cells make the

substance and how it works are not known, but " it may be a good

candidate for a microbicide " -- a vaginal gel that a woman could use

to prevent infection, Iqbal said.

A researcher from Mount Sinai School of Medicine, Arevik Mosoian,

described a substance called prothymosyn alpha that is produced by

certain immune-system cells and that appears to suppress HIV's

ability to replicate.

She said it is uncertain whether this is the same substance, called

CAF, that Jay Levy at the University of California at San Francisco

found years ago and which has eluded complete identification since

then.

Lund of the University of Toronto described another molecule,

called globotriaosyl ceramide (GB3), that appears to make it more

difficult for HIV to attach to a cell, which is the first step of

infection.

Cells lacking GB3 are highly susceptible to infection. Something that

enhanced or mimicked GB3's action could offer a new way to prevent

infection.

http://www.washingtonpost.com/wp-

dyn/content/article/2006/08/16/AR2006081601484.html