San Francisco Chronicle - Thursday, August 17, 2006
Sabin Russell, Chronicle Medical Writer

The 52-year-old El Dorado County landscaper has a robust supply of CD4s, the infection-fighting white blood cells that are ordinarily depleted in AIDS patients, and the level of HIV in her bloodstream is so low as to be virtually undetectable.

In the new parlance of AIDS researchers, she is an "elite controller," a person who is infected with HIV but able to control the virus completely with her own immune system.

Scientists at the 16th International AIDS Conference in Toronto would love to know her biological secret, and researchers in Boston and San Francisco are leading a global effort to find more people like her. Their goal is to find a common thread in the genes of elite controllers or in the viruses that still lurk in their bodies that might be the key to a new HIV treatment, perhaps even a vaccine.

"Somewhere inside there is a recipe for the end of the epidemic," said Harvard AIDS researcher Dr. Bruce Walker, director of the Partners AIDS Research Center at Massachusetts General Hospital.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Wednesday that the research could be promising but that it's too early for optimism. He said the federal laboratory is also looking at elite controllers. The lab found that many of them carry an unusual gene, but studies have yet to reveal what, if any, importance the gene may have.

"I believe we should get out and study elite controllers, but we should be conservative in what we expect from this research," he said. "This is still a very problematic and enigmatic virus."

Patients like Willenberg are quite rare -- perhaps 1 in every 300 people infected with HIV -- but Walker has gradually amassed a cohort of 100 of them willing to have their blood and tissues sampled for scientific study. The patients are hard to find, because they are not ill and hence often have little contact with physicians who study the deadly progression of HIV.

So on Wednesday, Walker formally announced the creation of the HIV Elite Controller Collaborative Study, which will attempt to recruit up to 1,000 such patients from around the globe. He also plans to sign up a similarly sized group of healthy but infected patients who have slightly higher detectable levels of virus in their bloodstream but, without taking any medications, have levels so low that they are symptom-free.

To gather such a large group of rare patients, Walker is teaming up with doctors at 15 other major AIDS research centers. Among the participating scientists is UCSF researcher Dr. Steven Deeks, who has been studying a population of 60 elite controllers at San Francisco General Hospital.

"Bruce and I independently started focusing on elite controllers for different reasons," Deeks said.

Walker is running sophisticated genetic tests on his pool of patients to determine if there is a common genetic trait among them that allows them to control HIV. Deeks is studying the genetic fingerprints of the viruses, painstakingly recovered from elite controllers, to see if there are weaknesses or flaws in the viral strains that infected these fortunate patients.

"We want to see if the virus is unique, damaged, crippled or cannot replicate," Deeks said.

Deeks also has about 60 patients who remain healthy because their viral load -- the number of detectable viral particles in a sample of blood -- is below 2,000 copies and remains stable without the help of AIDS drugs.

Scientists have long conducted studies on rare patients known as "long-term nonprogressors," who are infected with the virus but never become ill. Elite controllers are similar but are uniquely characterized by levels of infection that are so low that the virus cannot be detected by standard tests.

In November, Deeks and his team of researchers reported in the Journal of Virology that a group of elite controllers he included in a study had unusual concentrations of highly specialized CD4 cells that appeared to be toxic to HIV. While CD4s are a prime target of the virus, these unusual varieties produced high levels of virus-fighting proteins interferon and interleukin-2.

Initially, he had recruited a small number of elite controllers for comparison purposes in a study of patients who had drug-resistant virus but nevertheless remained healthy. "We then made some fascinating findings in this new group and have since focused more specifically on these unique and rare patients," Deeks said.

"As often happens in science, one makes important discoveries more or less by accident."

Walker said almost all AIDS physicians with large practices have one or two elite controllers among their patients, but until now, no one has tried to recruit them in large numbers for major studies. "We weren't getting any closer by studying 25 or 50 patients," he explained. To find common genetic traits in a scientifically meaningful study, large numbers of patients are required.

It was at meetings such as this one in Toronto that Walker came to realize that elite controller patients could be found in larger numbers, if a concerted effort was made to recruit them. "I'd be in a room with 500 physicians and would ask if they've had such a patient. About half their hands went up," he said.

Fueled by a $2.5 million grant from the Mark and Lisa Schwartz Foundation, he organized the collaborative study and has stepped up recruitment. So far, he has signed up about 200 elite controllers.

Willenberg learned of Walker's work with elite controllers two years ago and eagerly volunteered. She wanted to solve the mystery of her infection without illness. She flew to Boston to donate a pint of blood for the research and has since donated tissue samples and billions of her white blood cells through a plasma filtering process.

She is mystified by her rare status and awestruck that a solution to the AIDS crisis might exist in her bloodstream. "I hope that eventually we will be able to turn the key to that mystery," she said. "I'm walking on a path now I wish I'd taken 14 years ago."

Seeking subjects

Scientists searching for treatments or a vaccine for AIDS want to sign up "elite controllers," people who are infected with HIV but whose bodies control the virus to the point that it is virtually undetectable, for a study. Details about enrollment in the study are available at: www.massgeneral.org/aids/hiv_elite_controllers.asp.

E-mail Sabin Russell at srussell@sfchronicle.com.
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