| GMCarter 2006-09-26, 8:20 am |
| http://www.gmhc.org/health/treatment/ti/ti19_12.html#6
Who are the Elite Controllers?
By Bob Huff
Who are the elite controllers? No, they're not initiates of Yale's
secretive Skull and Bones Society or members the Trilateral
Commission. Elite controllers are people infected with HIV who have
been able to suppress their virus without using antiretroviral
medications. And Dr. Bruce Walker of Boston wants to meet them and
find out how they do it.
It's been appreciated for many years that some people with HIV do not
progress to AIDS at the same pace as most. Typically, the immune
damage of untreated HIV infection will lead to life threatening
opportunistic infections within eight to 12 years. But some people
have been infected for 20_25 years or more and have not yet
experienced the severe loss of CD4 immune cells that signals AIDS.
These people have been termed long-term nonprogressors, and in the mid
1990s, researchers began studying them to try to understand why some
people progressed to disease and others didn't. The ultimate hope was
that whatever protective qualities these people carried naturally
could be stimulated in everyone. There are also other long-term
survivors of AIDS who have experienced immune damage but have managed
to thwart the virus with treatments, although these people may also
have had help from their immune system or a genetic resistance to HIV.
For Walker and colleagues at the Partners AIDS Research Center who are
coordinating the study, duration of infection is not the main
criterion; they are looking for anyone who can control their HIV
without drugs. Elite controllers are defined as people with
asymptomatic HIV infection not taking antiretroviral therapy (ART) who
have experienced at least one year with HIV RNA below 50 copies/mL
(undetectable). Participants must have at least three sets of test
results documented within one year. Occasional viral load blips up to
1,000 copies/mL are allowable.
Walker estimates that there may be 1,500 or more elite controllers in
the United States. The research group has already collected blood from
over 100 people and has set a target of enrolling 1,000 elite
controllers into the study. They are also interested in finding a
similar group of people with asymptomatic HIV infection who, while not
undetectable, do manage to keep their HIV RNA levels under 2,000
copies/mL without drugs. Walker calls these people, who may be much
more common, viremic controllers. A long list of prominent HIV
physicians have signed up to scout for elite controllers, but
individuals who think they fit the criteria can contact Walker's group
in Boston directly to submit a blood sample.
The study plans to use gene sequencing techniques of the Human Genome
Project to construct a haplotype map for each participant, in hopes of
identifying genetic factors that may be contributing to their ability
to control HIV infection. A haplotype map allows scientists to look
for variations in genes as they are commonly organized on the
chromosomes. Advanced data analysis will evaluate if multiple gene
variants are possibly associated with spontaneous control of HIV.
Genetic sequencing and data analysis will be performed at the Broad
Institute in Boston. Additionally, high resolution HLA typing will be
conducted to look for genetic differences in these immune markers, and
adaptive immune responses and antibody studies will also be performed.
The entire genome of each person's virus will also be sequenced to see
if some viruses are more controllable than others.
These new genetic tools allow researchers to take the closest look yet
at what might make those lucky few who can control their HIV without
drugs different from everyone else. If they can uncover some
previously unrecognized protein or mechanism that is common to all
elite controllers, then the next step will be to look for a drug than
can safely produce the same effect in everybody else.
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