Genetic Analysis Offers Insights Into AIDS Resistance

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The new study searched for genetic differences that might explain variations in viral loads.

"One of the big questions in HIV is what are the determinants of the great variability in individuals being able to handle the virus. That's a big, big open question," Fauci said. "One of the ways to address that is to say look, there are some people whose viral set point, the level at which the body holds the virus in the absence of therapy, that varies enormously from person to person. We have no idea why that's the case. This study came up with three gene polymorphisms which appear to be associated very strongly with the ability to set the viral load. The combination of those explains about 15 percent of the variation in viral load among patients."

"The approach that we've taken is to use these natural differences among individuals in how well they can control the virus after infection as a pointer to new ways to act against the virus," Goldstein said. "That variation is huge. Some can push viral levels so low they will never progress to AIDS, whereas others can hardly contain it."

It took the international team of geneticists 18 months to identify the three crucial genes. In the end, they identified 486 appropriate patients from a possible universe of 30,000 people worldwide, and did genome-wide scanning on these patients. The study participants could not be undergoing treatment (as this would affect viral load levels), they had to know when they became infected, and there had to be high-quality laboratory estimates of their viral load.

This was the first time a genome-wide approach has been used for an infectious disease, the researchers said.

Two of the gene variants -- or polymorphisms -- were found in genes controlling the human leukocyte antigen (HLA) system, which helps identify foreign invaders and tags them for destruction. These genes, HLA-A and HLA-B, are switched off by HIV when it enters the body so the immune system is no longer able to recognize the virus as foreign.