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Los Angeles Times Examines HIV-Positive "Controllers," Studies, Research Difficulties

July 6, 2006

The Los Angeles Times on Thursday examined HIV-positive "elite controllers" -- people whose immune systems for long periods of time have been able to keep HIV at undetectable levels without using antiretroviral drugs -- and "viremic controllers" -- HIV-positive people whose immune systems have kept the virus at barely detectable levels without using antiretrovirals -- and the difficulties of conducting research on such individuals. According to the Times, elite controllers are "extremely rare" and account for about one-third of 1%, or about 2,000, known HIV-positive people. Researchers believe it is "unlikely" that elite or viremic controllers can infect others with HIV, the Times reports. "I would say we still don't have the faintest idea why these people are doing as well as they are," Bruce Walker, director of Partners AIDS Research Center at Massachusetts General Hospital, said, adding, "Achieving the state that these guys have reached in their bodies -- if we could do that through some intervention, we would solve the AIDS epidemic."

To learn why and how HIV remains at extremely low levels in controllers, researchers are studying both the innate immune system -- which provides a "general response" that immediately activates to "dismantle" incoming pathogens -- and the adaptive immune system -- which is a longer-term response that relies heavily on antibodies, including CD4+ T-cells -- according to the Times. Steven Deeks of the University of California-San Francisco and colleagues assembled a group of 50 elite controllers to analyze their adaptive immune systems and found that half of the controllers fought the virus through a "powerful response by T-cells," and the other half showed no T-cell response, the Times reports. "The 25 people in our cohort who have no T-cell reaction can provide insight into whole new ways of thinking," Deeks said, adding, "There are 25 guys who have no reason for controlling the virus." In a related study, Jay Levy of the University of California-San Francisco and colleagues focused on the infection-fighting tools of the innate immune system to identify antiviral proteins found in controllers, the Times reports. Controllers show that the immune system is able to contain HIV naturally, Levy said, adding, "This has been a long time coming, but in my opinion we can look forward to long-term survival without toxic drugs."

Research Difficulties
Some researchers believe that controllers are able to contain HIV because the strain of the virus with which they are infected is defective, the Times reports. To study every controller for defective HIV would be "prohibitively expensive," Deeks said, adding that if such a study were initiated, 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." Another problem with studying controllers is that there are not enough of them to assemble local cohorts large enough to study effectively, the Times reports. Walker and his research team at Massachusetts General Hospital have assembled 76 elite controllers and 100 viremic controllers from across the country to participate in a new study. "Basically, we want to recruit every single one of these people in the [U.S.]," Walker said, adding, "We have to have a large enough sample to begin to see patterns in this population" (Ricci, Los Angeles Times, 7/6).

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