Another common sentiment among them was a desire to be studied. "The question seems to come back to them all the time," said Pereyra: "Why me? What's so special about me?"
To divine the answer, researchers are, among other efforts, probing the body's so-called innate immune system, trying to discern if controllers harbor a defective form of the virus and undertaking an unprecedented study of hundreds of controllers in an attempt to learn if there is anything genetically unique about them.
Human beings have two immune systems, the innate and the adaptive. The innate system is a general response to any incoming pathogen, and it can kick in almost immediately. Its component cells, including some known as "natural killer cells," dismantle viruses, kill off early cancer cells and engulf and eliminate foreign bacteria.
The adaptive system, which is dependent largely on infection-fighting T-cells and antiviral antibodies, is more finely tuned and needs to identify an invader precisely before going into action, a process that takes days or weeks. Thus far, the great bulk of HIV research has centered on the adaptive system.
Researchers at UC San Francisco have assembled a group of 50 elite controllers (including Traywick), and research on them has produced an intriguing discovery.
About half of the elites control the virus, as expected, through a powerful response by T-cells.
The other half shows no such T-cell response.
"The 25 people in our cohort who have no T-cell reaction can provide insight into whole new ways of thinking," says Dr. Steven Deeks, a prominent HIV researcher at UC San Francisco. "There are 25 guys who have no reason for controlling the virus."
Because their adaptive immune systems appear to play little or no part in controlling the virus, they are prime subjects for investigation into the innate immune system.
Since 1984, Dr. Jay Levy, director of the Laboratory for Tumor and AIDS Virus Research at UC San Francisco and one of the first to isolate HIV, has focused on the innate immune system and its unique infection-fighting tools.
In all of the controllers he has tested, Levy found evidence of an effective antiviral protein secreted by certain innate immune system cells. Over the last two decades, he and his team have searched through the thousands of proteins these cells make in the hope of identifying the antiviral protein. They've managed to narrow the number to about 80, but they need to winnow it further.
They've also been trying to identify the gene that causes controllers' cells to express the antiviral protein. Of the body's 37,000 genes, Levy's team identified, through several experiments, eight that look promising; they expect to identify five or six more.
Eventually, they'll introduce the most promising genes into human cells and look for the antiviral protein activity.
Levy is also looking at another tool of the innate immune system, a small number of cells that produce virus-crippling interferon. He has found that controllers have higher numbers of these cells than even healthy HIV-negative people.
Essentially, controllers show that the human immune system is capable of containing HIV naturally, Levy said. "This has been a long time coming, but in my opinion we can look forward to long-term survival without toxic drugs."
Some researchers have theorized that controllers are able to contain the virus because the strain of the virus they're infected with is somehow defective. Although the current belief is that a defective form of the virus does not in itself explain controllers' success -- it might even be that the virus is capable of repairing itself -- researchers haven't been able to tease the virus out of some elite controllers so that it can be examined for defectiveness.
"Whenever researchers find the virus, it usually looks normal," Deeks said. "But some of the people in whom it can't be found, it may be they were exposed to a defective virus."
To examine every controller for defective virus would be prohibitively expensive, he said. If such a study were mounted, he said, the idea would be "to see if the virus is there and if it is defective, because in theory that virus will give good insights into making an effective vaccine."
One of the problems with studying elites is that there are so few that researchers haven't been able to assemble local research cohorts large enough to study effectively. Now, however, Walker of Massachusetts General and his collaborators hope to collect blood samples from 500 to 1,000 elite controllers and a similar number of viremic controllers, subject them to detailed genetic analysis and compare the findings with those from two groups: HIV-negative people and HIV-positive people in whom the virus has progressed.
