August 18, 2006

Study to probe why some with HIV don’t get ill

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Study to probe why some with HIV don’t get ill

Vanderbilt University Medical Center is participating in an international study to find out why some people infected with the AIDS virus don't get sick.

“We're using the power of genetic sequencing to see whether there are any genetic fingerprints that we can find in people that allow them to control the virus,” said Spyros Kalams, M.D., director of viral immunology studies in the Vanderbilt Infectious Diseases Unit.

The study, coordinated by the Partners AIDS Research Center (PARC) at Massachusetts General Hospital, was discussed Wednesday at the 16th International AIDS Conference in Toronto.

Called the HIV “Elite Controller” Study, the project is the first to use large-scale haplotype mapping in people infected with the human immunodeficiency virus (HIV) to search for genetic factors that enable some of them to control the virus without treatment, sometimes as long as 25 years after infection.

“If we could discover how these individuals can coexist 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 PARC director Bruce Walker, M.D., an initial organizer of the study, in a news release.

Researchers have known for years that a small percentage of people infected with HIV — probably less than 1 percent — are able to control the spread of the virus without treatment.

Patients who are being treated for HIV infection may have 50,000 copies of the virus in every milliliter of their blood. That is their viral “load.”

In comparison, “controllers” — people who can control the infection without treatment — have viral loads below 2,000 copies per milliliter, and “elite controllers” have viral loads too low to be detected by currently available assays.

These people may have more robust immune systems, said Kalams, who first started investigating the phenomenon in 1991, when he began his infectious disease research fellowship under Walker.

An associate professor of Medicine who joined the Vanderbilt faculty in 2002, Kalams is co-principal investigator of the Vanderbilt HIV Vaccine Trials Unit, and immunology core director of the Vanderbilt-Meharry Center for AIDS Research.

During the past four years, Kalams and his colleagues have identified nearly 30 HIV controllers, and they are continuing to recruit subjects into Vanderbilt's HIV Controller Study.

The Vanderbilt group and others have found that two human leukocyte antigens (HLA) — immunological markers known as B57 and B27 — correlate with the ability to control HIV infection.

Only about 8 percent of the general population carries the gene for HLA B57. In the controllers enrolled in the Vanderbilt study, however, it's found about 60 percent of the time.

“It's not completely protective,” Kalams said, but “if you have HLA B57, you have a very high likelihood of being able to control the virus.”

While it's unlikely that the B57 gene alone is responsible for the protective effect, researchers now have the tools to begin to unravel the mystery — thanks to the sequencing of the human genome and the subsequent mapping of human “haplotypes,” sets of closely linked genetic markers that tend to be inherited together.

The Elite Controller Study is recruiting HIV-positive adults, age 18 to 75, who have maintained viral loads below 2,000 copies without taking HIV antiviral medications. A small sample of blood will be taken from participants, whose identities will be strictly protected.

Genetic sequencing will be conducted to determine which genes are associated with control of the virus.

Participants in Vanderbilt's HIV Controller Study can sign an additional consent form for genetic studies to enroll in the Elite Controller Study. An extra blood draw will not be required.

For more information on the study, contact Valerie Mitchell at 467-0154, extension 120 or e-mail