A FIELD OF RESEARCH THAT HAS BECOME accustomed to failure and disappointment” is how Protocharacterized HIV/AIDS in its Winter 2009 story “The Rare Few”. Recently, however, scientists have found two causes for optimism.

In November, the Norwegian pharmaceutical company Bionor Pharma announced that in trials, a vaccine-like drug, Vacc-4x, significantly reduced the amount of HIV present in AIDS patients. The drug works by stimulating an immune system response to an artificially modified protein that bears similarities to the HIV virus. Although it does not represent a cure, the drug seems promising in slowing the disease.

Also in November, researchers reported the discovery of another potential route to therapy. For nearly 20 years, physicians have been aware of an extraordinary group of people: HIV-positive individuals who never seem to experience symptoms of the disease or to develop AIDS. Yet when Proto covered the phenomenon barely two years ago, researchers still had little idea what molecular factors set apart these so-called elite controllers—about one in 300 infected people.

One of many theories studied was the idea that elite controllers possess a genetic trait that confers immunity to HIV. Yet testing this idea would require combing through the human genome’s 3 billion pieces of coded information to look for that trait. Scientists conducting the International HIV Controllers Study reported in the online version of the journal Science that this seeming needle-in-a-haystack search had produced spectacular results. “We found that it was basically five amino acids that made the difference between someone who controls and someone who doesn’t,” says Bruce D. Walker, director of the Ragon Institute of MGH, MIT and Harvard, and leader of the study.

Those amino acids are contained in genes that encode human leukocyte antigens. After a virus enters a cell, these antigens carry pieces of the virus to the cell’s surface to put them on display. The display serves as a distress signal to the immune system, which dispatches T cells to destroy the infected cell. Although it’s still unknown why the immune system usually fails to stop AIDS and other deadly viruses, researchers for years have been investigating HLA genes as a possible key.

Scientists don’t yet know what the variations mean, though they did detect in elite controllers a distinct shape in the part of the antigen that binds to the virus, possibly helping it successfully flag the virus for destruction.

The news heartens the hundreds of elite controllers who have donated blood to research. Karen Pancheau has lived with the virus since receiving a tainted blood transfusion in 1982. “If I can even in some minute way make other people’s lives better,” Pancheau says, “then I have a moral obligation to do what I can.”