Some with HIV go years without symptoms; the question is why?
Pamela Neely (above), contracted HIV like many in her neighborhood. However, she has never exhibited symptoms of the illness. (Jori Klein / Globe Photo)
They had a name for the killer stalking Pamela Neely's neighborhood in New York: "They called it 'the monster,'" Neely said.
"People lost facial muscle, their backs hunched over, their hair became fine. It was able to take complete control over their lives, and they went very, very quickly." The monster was AIDS. It killed many of the intravenous drug users Neely knew.
"Let me think 200? 300?" she said. "I stopped going to funerals. I can't go anymore. I can't. Every time I turn around, somebody else has died."
Neely, 47, has the virus, too. She first tested positive on April 29, 1993, and figures she caught the bug sometime in the '80s, when sorrow over her mother's death caused her to seek the illusory comfort of cocaine and heroin.
But Neely has never had a single symptom. Not one. And her immune system remains doggedly robust all on its own, without the help of medication.
As she watched those around her perish, she posed a single, simple question: Why have I lived when others died?
Now a team of scientists, led by a researcher at Harvard Medical School, wants to answer the same question.
There are roughly 2,000 people nationwide, like Neely, who are infected with HIV but whose bodies have controlled the virus for years, even decades. In the lives of those people, dubbed "elite controllers," researchers hope to find clues that will help them develop drugs or vaccines, clues that have eluded them for 25 years of searching and billions in spending.
"In the beginning, no one realized how complex and tricky the disease and the virus were going to be," said Mary Carrington, a geneticist at the National Institutes of Health. "But if we can understand why these rare individuals are able to control the virus, can we help other people live with the virus?
"I hope so, because these two-and-a-half decades have really shaken us."
This medical detective story began June 5, 1981, when federal disease trackers first reported a curious cluster of pneumonia cases among five gay men in Los Angeles. Since then, the human immunodeficiency virus has decimated a generation in Africa, redefined human sexuality, and reinvigorated the hunt for pills and shots to thwart all manner of viruses.
In the early days of the epidemic, it seemed as if everybody with AIDS was dying within months of diagnosis. Then researchers began to notice a few exceptions.
"We said, 'Holy Toledo. What's going on? Some of these people are still walking around, completely healthy,'" said Paul O'Malley, who was involved in early tracking of the disease.
To understand why those few thrived when so many others died, researchers decided to examine blood samples of gay men collected a decade earlier as part of a study of hepatitis B, a disease that, like AIDS, can be transmitted by sex or sharing drug needles, said Dr. Susan Buchbinder, HIV research director at San Francisco's Department of Public Health. The samples showed that the survivors' immune systems had been activated by the presence of the AIDS virus, but medical exams found none of the classic signs of the disease: no fever, no pneumonia, no opportunistic infections.
Dr. Bruce Walker, a leading AIDS researcher at Harvard and Massachusetts General Hospital, was enlisted in the early 1990s to analyze the blood of those men.
He and his colleagues found that the patients' success in controlling the virus almost certainly had nothing to do with the virus itself. There was no evidence that they were, say, carrying an especially feeble form of HIV.
This meant that the answer must reside in the patients most likely in their genes, especially those involved with letting the virus enter human cells or in those governing the body's immune response.
"These people are showing us that there is some way to coexist with the virus," Walker said. "What we need to figure out is how the heck they are doing it."
Scientists already know, for example, that certain people of Northern European descent possess a genetic quirk that inhibits HIV from invading their cells which could be one factor in saving people from symptoms.
Dr. Jay Levy, an AIDS specialist at the University of California at San Francisco, said his research group knows of a half-dozen patients who have kept the virus in check for nearly three decades.
"They will say, 'Why am I able to be in this category?'" Levy said. "My quick answer is: 'You chose the right parents. Essentially you have a genetic background that allows you to control this virus."'
Conventional tools of disease research failed to find a genetic smoking gun, so Walker came up with an idea: Let's track down as many of the elite controllers as possible and perform detailed genetic analyses on them, using the fruits of recent advances in mapping human genes.
To do that requires tenacity, collaboration and money.
The tenacity comes in the form of phone calls, e-mails, and trips across the country to meet with doctors and implore them to identify elite controllers in their practices. In March, for example, Walker found himself at a conference in New York's Times Square speaking to about 500 AIDS specialists.
"I asked them to raise their hands if they had someone like this in their practice. About half of the hands in the audience went up," Walker said. "The doctors said, these patients kept asking me, 'Is there anything I can do to help?"'
The collaboration came in the form of a network of scientists who decided to provide their expertise to Walker. There's Carrington in the federal government. She will be looking at one vital gene that alerts the immune system when cells become infected with HIV.
And, among others, there's Eric Lander of Cambridge's Broad Institute, one of the fathers of the quest to map the human genome. He will examine the patients' genetic fingerprints, hunting for characteristics that the elite controllers share.
Then there's the money.
Typically the pursuit of grants to underwrite this kind of research would involve completing reams of applications and meeting with government authorities or leaders of charitable foundations.
But all Walker had to do was mention it to two people: Mark and Lisa Schwartz. A few months back, Walker described his desire to track down at least half of the 2,000 elite controllers to Mark Schwartz, a successful investment banker with a history of underwriting AIDS research.
Schwartz and his wife donated $2.5 million of their own money to Walker's quest. "This seemed like a very powerful idea and very fruitful to study," Schwartz said. So far, Walker and his collaborators have made contact with about 200 elite controllers nationwide, including Neely.
She read about the hunt for patients in a magazine called Poz that's targeted at people who are HIV positive.
"I literally dropped the magazine and said, Oh, my God. That's something for me," said Neely, now drug-free and an AIDS counselor.
Over the years, she said, she has been tested 10 to 15 times to make certain she really is infected with the virus. Those tests were positive, but just as surely, other tests showed that she has a copious army of disease-fighting warriors known as T-cells.
"When I tell them my count, everybody says, 'Give me some of those T-cells, girl,'" Neely said. "I wish I could. I really wish I could."