New Clue To Slower Progression Of AIDS

Date: Sep-23-2012The average time from HIV infection to full-blown AIDS in the absence of treatment is about 10 years, and while some people succumb much sooner,
others, known as the "slow progressors", can remain healthy for another 20 years or more. Now scientists at the University of California, Los Angeles (UCLA),
believe they may have uncovered a new clue as to why.

They found HIV-infected people who carry a gene variant that causes the immune system to attack a particular section of a virus protein are more likely to be
among the slow progressors.

The team, from the Multi-Center AIDS Cohort Study (MACS) in the UCLA AIDS Institute, report their findings in the October print issue of the Journal of
Virology.

Scientists already know that a gene variant called HLA-B*57 (B57), present in under 5% of the general population, is carried by 40 to 85% of slow progressors.
But even among those who carry this variant, speed of progression to AIDS can vary enormously.

Previous studies have shown that HLA-B genes activate killer T-cells in the immune system that recognize sections of proteins or epitopes in HIV. But it was not
clear which. Also, much of the knowledge was derived from working on T-cell response after several years of infection.

But the senior investigator on this new study, Beth D. Jamieson, a professor of medicine at the Geffen School of Medicine, and her colleagues, were of the view
that the most critical responses are the ones that occur early during infection, which is the time when T-cells are still strong, and can make it hard for HIV to find
places to hide in the body.

However, studies are further complicated by the fact that even if you study the immune responses in the early stages, you can't predict during these periods
which people will eventually turn out to be slow progressors, making it very difficult to correlate immune responses with long-term outcomes.

This is where the Multi-Center AIDS Cohort Study (MACS) comes in: they have been freezing blood samples of thousands of men infected with HIV or at risk of
becoming infected, every six months since 1984.

Having available such an incredibly long series of data points, good caretaking of frozen samples, accompanied by careful documentation of the health of
participants, allowed the researchers to access blood samples from 14 people carrying the HLA-B57 gene taken shortly after HIV infection , along with their
infection dates, and details of long-term outcomes.

Lead author Catherine Brennan, an assistant research scientist in the department of medicine at the David Geffen School of Medicine at UCLA, told the
press:

"This allowed us to correlate early immune responses with long-term outcomes."

Jamieson explained that it was important compare killer T-cell responses only among the B57 variant carriers, rather than responses of carriers versus non-carriers.

"Since possession of the B57 variant is not sufficient, we wanted to determine what specific immune events in B57 carriers are associated with immune control of
the virus," she said.

"We found that those who targeted the IW9 epitope early in infection had significantly longer times until onset of AIDS than those who did not. The
finding that targeting of IW9 seems to be important is novel, as this epitope had been overlooked in many earlier studies of B57 and HIV," she added.

Although pleased with their findings, the team cautions that they should be treated as tentative, since the results come from only a small sample of 14
individuals.

They recommend repeating the study with a much wider pool of individuals.

They also point out that their findings merely propose a link: they do not suggest a cause and effect relationship.

The authors conclude:

"This work, although not powered by a large cohort and necessarily exploratory in nature, does suggest that the role of IW9 targeting in B57-mediated protection
merits closer attention."

"Understanding the detailed mechanisms by which B57 is associated with slow progression to disease will reveal underlying principles of immune control of
HIV-1, which is critical for the development of rational vaccine-design strategies" they add.

Written by Catharine Paddock PhD

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