People who naturally control HIV long-term without antiretroviral drugs -- estimated at about one in 300 people infected with the virus -- have a distinct pattern of amino acid variations in genes encoding HLA proteins, which enable the immune system to recognize and respond to invading pathogens and virus-infected cells.

As reported in the November 4, 2010, advance online edition of Science, investigators with the International HIV Controllers Study performed a genome-wide association analysis that included nearly 1,000 HIV controllers and 2,600 people with normal progressive HIV disease. The researchers identified several specific amino acid substitutions in the HLA-B peptide binding groove that were associated with protection against disease progression.

These results, the researchers suggested, imply that the interaction between HLA and viral peptides is a key to durable control of HIV. "We found that, of the three billion nucleotides in the human genome, just a handful make the difference between those who can stay healthy in spite of HIV infection and those who, without treatment, will develop AIDS," said Bruce Walker from the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard. "Understanding where this difference occurs allows us to sharpen the focus of our efforts to ultimately harness the immune system to defend against HIV."

"HIV is slowly revealing its secrets, and this is yet another," he continued. "Knowing how an effective immune response against HIV is generated is an important step toward replicating that response with a vaccine. We have a long way to go before translating this into a treatment for infected patients and a vaccine to prevent infection, but we are an important step closer."

Liz Highleyman ( is a freelance medical writer based in San Francisco.