POZlife

POZLife: Life from the Infected and Effected point of veiw.

AIDS immunity under the microscope

Posted by pozlife on August 17, 2006

CAROLYN ABRAHAM

From Thursday’s Globe and Mail

One in every 300 people living with HIV never becomes sick or needs to
take even a single drug to fight their infections, according to a
surprising statistic released at the International AIDS Conference on
Wednesday.

Researchers have long known that some people have a natural resistance
to the AIDS virus. But only now, 25 years into the epidemic, are they
discovering the scope of a phenomenon they’re calling “elite
controllers.”

These are people with HIV who have the mysterious ability to stop the
virus from replicating, even without medications. An international
research consortium is now anxiously recruiting elite controllers for a
new genetics study.

“If we could discover how these individuals can co-exist with
this virus without damage to their immune system and could find a way
to replicate that ability in others, we would have a recipe for halting
the HIV epidemic,” said Bruce Walker, a professor at Harvard
Medical School and one of the study’s key organizers

“There is a reasonable chance we will come up with something very
important with this,” said Dr. Walker. “We need
patients…. We need to get the word out.”

Researchers have to enroll at least 1,000 elite controllers in order to
make sure they have enough numbers to make meaningful genetic
discoveries. About 200 patients are expected to be recruited from
Canada, where 25 patients have already signed on.

Rafick-Pierre Sékaly, a McGill University immunologist and study
investigator, said the Canadian subjects have been HIV positive for
seven to 15 years but are healthy and have never required treatment.

In most people infected with HIV, the human immune system cannot stop
the virus from replicating without medication. In the absence of
treatment, HIV makes so many copies of itself it eventually overwhelms
the host’s immune cells and the person grows sicker.

But an elite controller has fewer than 50 copies of HIV per millilitre
of blood, Dr. Sékaly said. This is a level considered
undetectable by current tests. Researchers also hope to recruit 1,000
so-called ‘viremic controllers.’ These are healthy people whose
blood samples show 2,000 viral copies or less.

The researchers had stipulated at the outset that subjects had to be
infected for at least a year to qualify for study enrolment. But
doctors have found the 200 patients enrolled so far have lived
sickness- and treatment-free with HIV for an average of 15 years.

“You’re sitting across from these patients,” said Dr.
Walker, “and you just feel like, oh, the answer is there right in
front of you, we’ve just got to fish it out of them.”

He also guessed it was unlikely that these people would ever see their
infections progress, and that they would, in the end, likely die of
something other than AIDS.

Loreen Willenberg, a 52-year-old landscape designer from Diamond
Springs, California, learned in 1992 that she was HIV positive. Since
then she has battled the emotional impact associated with the stigma of
having HIV in a small town, and opted only to “come out”
with her HIV status earlier this year.

But the disease, she said, took no physical toll: “I’m in perfect
health,” Ms. Willenberg told a press conference Wednesday.
“I’ve maybe had one cold in 14 years.”

In response to a journalist’s question about her diet, Ms. Willenberg
said she eats many fruits and vegetables, but that she is not a
vegetarian. She added that she is not a fast food eater and never has
pop or candy in the house.

But Dr. Walker noted other elite controllers in the study eat fast food “non-stop.”

The test subjects also do not have in common any of the genetic traits
known to be associated with HIV resistance, said Dr. Walker, who is
also director of the Partners AIDS Research Center at Massachusetts
General Hospital.

Neither have these elite controllers “contracted some wimpy form
of this virus,” Dr. Walker said. Some of these protected patients
know who infected them and those people have gone on to get ill. But
researchers still plan to sequence the DNA of the viruses infecting
them.

It is unknown at this point if any elite controllers have ever passed
on HIV. But having a low viral load is believed to significantly reduce
the chance of transmission.

Doctors have long remarked on the puzzle of the patients, also known as
“long-term non progressors.” But it wasn’t until the
mid-1990s when viral-load testing became available that researchers
were able to clearly identify people who could keep HIV in check.

Dr. Walker said that a majority of these elite controllers have not disclosed that they are HIV positive.

“They also feel a sense of guilt because they are
survivors,” Dr. Sékaly said. “They have seen their
friends die and they have never even been sick.”

Ms. Willenberg once wrote an article on her strange condition,
entitled, “Partially HIV Positive.” “She didn’t feel
like she belonged to the infected or the uninfected,” said Dr.
Walker.

Dr. Walker estimates that 2,000 people in North America are elite
controllers. But he suspects the one-in-300 number applies to HIV
infected people all over the world. Research in South Africa, he said,
indicated a similar finding.

Just recently, Dr. Walker said, he gave a course to 500 doctors who
treat AIDS patients and asked how many had elite controllers in their
practice. “Half the hands in the room went up,” he said.
“Then I asked, “what have you done with [them or this
information] and they throw their hands up in the air … no one
knows.”

Among the theories researchers are considering is that elite
controllers may have natural anti-viral factors in their cells. It
could be that the immune system of the elite controllers offers up a
weaker immune response to HIV, preventing the body from over-killing
its own T-cells. But all of these things are likely to be effected by
genetic traits.

The study team plans to take blood and DNA from study participants and promises strict confidentiality.

Their genomes will be scanned for mutations already identified in the
Haplotype Map. That map spun off the human genome project and
pinpointed the most common gene mutations in four different ethnic
populations. The McGill team will then analyze the function of the
important traits they find.

“One of the key problems with the development of a
vaccine,” said Dr. Sekaly, “is that we don’t know what
response to mimic.”

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