Who Are the Elite Controllers?

Who are the elite controllers? No, they're not initiates of Yale's secretive Skull and Bones Society or members the Trilateral Commission. Elite controllers are people infected with HIV who have been able to suppress their virus without using antiretroviral medications. And Dr. Bruce Walker of Boston wants to meet them and find out how they do it.

It's been appreciated for many years that some people with HIV do not progress to AIDS at the same pace as most. Typically, the immune damage of untreated HIV infection will lead to life threatening opportunistic infections within eight to 12 years. But some people have been infected for 20-25 years or more and have not yet experienced the severe loss of CD4 immune cells that signals AIDS.

These people have been termed long-term nonprogressors, and in the mid 1990s, researchers began studying them to try to understand why some people progressed to disease and others didn't. The ultimate hope was that whatever protective qualities these people carried naturally could be stimulated in everyone. There are also other long-term survivors of AIDS who have experienced immune damage but have managed to thwart the virus with treatments, although these people may also have had help from their immune system or a genetic resistance to HIV.

For Walker and colleagues at the Partners AIDS Research Center who are coordinating the study, duration of infection is not the main criterion; they are looking for anyone who can control their HIV without drugs. Elite controllers are defined as people with asymptomatic HIV infection not taking antiretroviral therapy (ART) who have experienced at least one year with HIV RNA below 50 copies/mL (undetectable). Participants must have at least three sets of test results documented within one year. Occasional viral load blips up to 1,000 copies/mL are allowable.

Walker estimates that there may be 1,500 or more elite controllers in the United States. The research group has already collected blood from over 100 people and has set a target of enrolling 1,000 elite controllers into the study. They are also interested in finding a similar group of people with asymptomatic HIV infection who, while not undetectable, do manage to keep their HIV RNA levels under 2,000 copies/mL without drugs. Walker calls these people, who may be much more common, viremic controllers. A long list of prominent HIV physicians have signed up to scout for elite controllers, but individuals who think they fit the criteria can contact Walker's group in Boston directly to submit a blood sample.

The study plans to use gene sequencing techniques of the Human Genome Project to construct a haplotype map for each participant, in hopes of identifying genetic factors that may be contributing to their ability to control HIV infection. A haplotype map allows scientists to look for variations in genes as they are commonly organized on the chromosomes. Advanced data analysis will evaluate if multiple gene variants are possibly associated with spontaneous control of HIV. Genetic sequencing and data analysis will be performed at the Broad Institute in Boston. Additionally, high resolution HLA typing will be conducted to look for genetic differences in these immune markers, and adaptive immune responses and antibody studies will also be performed. The entire genome of each person's virus will also be sequenced to see if some viruses are more controllable than others.

These new genetic tools allow researchers to take the closest look yet at what might make those lucky few who can control their HIV without drugs different from everyone else. If they can uncover some previously unrecognized protein or mechanism that is common to all elite controllers, then the next step will be to look for a drug than can safely produce the same effect in everybody else.

For more information about this study, contact: Florencia Pereyra, MD, fpereyra@partners.org.