The Rare Few

22 WHAT are the oDDs? that you will never need drugs to keep your hiV in check? // that you will live longer than your doctor’s first prediction? his second? his third? // that you hold a vital clue to preventing, even curing, aiDs? The Rare Few by charles slack // PhotograPhs by gregory heisler t first Karen Pancheau figured her son whose samples showed they had been infected with HIV Tyler’s nasty rash came from friction on in the late 1970s; many had already died, but some weren’t A the mats at judo class. But when the rash even sick. Then, in 1994, Walker met a hemophiliac in Bos- began dissolving layers of flesh, his father ton named Bob Massie, who had become infected with HIV took the teenager for tests, which revealed through a blood transfusion in 1978—three years before he had HIV. Karen, too, tested positive AIDS was even identified as a disease. “People keep telling for HIV, the virus that causes AIDS, which she’d apparently me I’m going to die, and I keep living,” Massie told Walker. acquired from a blood transfusion in June 1982 and to which Walker immediately began to study his immune system. she exposed Tyler during childbirth and breast-feeding. Yet as A few years later, speaking before several hundred doctors Tyler slowly progressed to AIDS, Karen remained healthy. at an AIDS conference in New York City, Walker asked how Various drug cocktails kept AIDS from killing Tyler, but they many had run across similar patients. When at least half the left him constantly fatigued, and on Nov. 11, 2005, the 23-year- audience raised their hands, Walker realized that people like old committed suicide. Remarkably, 26 years after receiving Massie represented a real opportunity for research. He also HIV-tainted blood, Karen Pancheau has yet to develop AIDS. understood why these rare individuals—no more than one in She isn’t alone. Bruce Walker, now director of the Part- every 300 cases, or perhaps 5,000 of the more than 1 million ners AIDS Research Center at the Massachusetts General infected Americans—had remained so well hidden: “They Hospital and director of the Center for AIDS Research at weren’t sick. They weren’t coming to the hospital.” Harvard University, first became aware in 1992 that there Those protected few came to be called “elite controllers” were others like Karen Pancheau who seemed somehow because their ability to combat the virus puts them in excep- protected from AIDS. He learned about the phenomenon tional company among infected individuals. Their existence from Susan Buchbinder, an epidemiologist in San Francisco injects a note of hope into a field of research that has be- who was analyzing blood samples from homosexual men come accustomed to failure and disappointment since HIV taken years earlier (for the trial of a hepatitis vaccine) to was identified in 1981. Early on, drawing on the experiences understand how AIDS progresses. She started studying men of medical science with mumps, measles, smallpox and other protomag.com // Winter 09 < Solitary figures among legions of AIDs sufferers, “elite controllers,” such as Joseph o’brien of atlanta, test positive for HIV but never seem to get sick. Despite not having taken the antiviral drug aZt for more than a decade (and then only briefly), o’brien remains healthy. Winter 09 // protomag.com karen Pancheau Portland, ore. hiV positive since 1982 < the failure of its latest attempt at a vaccine, London’s Indepen- dent newspaper surveyed more than 35 leading AIDS researchers in the United States and Great Britain. About two-thirds 24 of those who responded said an HIV vaccine wouldn’t appear within the next decade. Several predicted a vaccine would never be developed. Against that gloomy outlook stands the relative handful of elite controllers, who, somehow, have managed to do what medicine’s best efforts have been unable to accomplish. No one yet knows how their bodies keep AIDS at bay. Are their immune systems exceptionally strong and effective? (One recently published study suggests that elite controllers have a heightened ability to kill HIV-infected cells.) Do they possess some elusive genetic trait that protects them? Or does a com- bination of still-unknown factors set them apart? As more and more elite controllers emerge—some 500 in the United States have so far volunteered for testing—scientists are hopeful that they will be able to uncover what shields these rare few from AIDS. And perhaps in the process they’ll find a way to safeguard everyone else as well. ike many other viruses, the human immunodeficiency virus does its damage by entering healthy cells, repro- L ducing and releasing copies of itself that then infiltrate other cells. The immune system fights back with several infectious diseases, researchers confidently predicted a vaccine mechanisms, including B cells, which produce antibodies that within five years. That hope faded as one high-profile effort coat invading viruses, thus preventing them from entering after another faltered and the death toll from AIDS mounted. other cells; and T cells, which find and dispatch infected cells. Since 1981 AIDS has claimed more than 25 million lives, and (There are two main types of T cells: CD4+ cells, which over- today some 33 million people worldwide are infected with HIV. see the immune response, and CD8+ cells, or “killer” T cells, Though pharmaceutical advances have greatly increased how which do most of the actual killing.) In the typical progression long many patients survive, those innovations have merely of HIV, a patient’s viral load—the number of viral copies per commuted what once seemed an automatic death sentence to milliliter of blood—creeps higher while the number of CD4+ a lifetime of battling a chronic disease. Unlike, say, a measles cells declines. When a patient’s T cell count falls to about 200 vaccine, which can be delivered to masses of people a single per milliliter of blood and an “opportunistic” infection (often shot at a time, AIDS medications are expensive and must be pneumocystic pneumonia or Kaposi’s sarcoma) takes hold, taken daily, creating a logistical nightmare for reaching the the patient is considered to have progressed to AIDS. poorer parts of the world in which AIDS proliferates. People with AIDS may have viral loads of several hundred Many scientists have openly questioned whether truly con- thousand copies per milliliter. In contrast, the viral loads of quering AIDS, with a vaccine or a cure, is even possible. In elite controllers range from a scant 50 copies per milliliter 2008, after pharmaceutical manufacturer Merck announced down to levels so small that even the most sensitive tests protomag.com // Winter 09 can’t detect them. Doctors know these people have the virus only because separate tests have revealed the presence of antibodies to HIV in their systems. In other words, elite controllers aren’t HIV-free; they may still be able to pass the virus to others, in whom it may be deadly. Two characteristics of HIV make the condition an im- mense challenge for the body—and vaccines—to combat. Most viruses attack particular parts of the body, with, for example, the common cold virus going after the nasal pas- sages and hepatitis infecting the liver. But HIV targets T cells 25 themselves, depleting the very system needed to fight disease. What’s more, unlike most other viruses, HIV can mutate rapidly into countless variations within a single patient, making it extremely difficult to develop an effective vaccine. “This isn’t just one virus,” says Dennis Burton, an immu- nologist at the Scripps Research Institute in La Jolla, Calif. “You’re talking about tens of thousands of different viruses.” Even worse, neutralizing one HIV variant simply creates a niche for other opportunistic mutations to fill. “HIV is really an elegant replicating machine built to evade almost every defense humans have against pathogens,” explains Steven Deeks, an HIV specialist at San Francisco General Hospital. arly on, researchers discovered that elite controllers aren’t infected with a less virulent strain of the disease. E But little else about their condition is certain, and that’s a situation Deeks, Burton, Walker and a growing number of other researchers are determined to change. Since 2006, Walker and his colleagues have been organizing an international contingent of more than 250 researchers and more than 200 physicians who have elite controllers as patients. Initially funded by a gift from Joseph o’brien the Mark and Lisa Schwartz Foundation atlanta, ga. hiV positive since 1992 Unlike most other and recently boosted by a $22 million grant from the Bill & Melinda Gates viruses, HiV can Foundation, the International HIV Controllers Study is work- ing to identify elite controllers, collect samples of their blood mutate rapidly into and DNA, and distribute the samples to labs for analysis. Burton, at Scripps, is studying the immune systems of HIV- countless variations positive people, some of whom are elite controllers but most of whom simply have low viral loads, whose antibodies are ca- within a single patient, pable of acting against many different strains of the virus. At making it extremely the MGH, Marylyn Addo investigates regulatory T cells, which prevent the immune system from destroying healthy cells in difficult to develop an its quest to quell invaders. Though her work is at an early stage, she is hopeful the comparison will eventually yield effective vaccine. clues about how elite controllers’ regulatory T cells maintain Winter 09 // protomag.com “rodney” Flagstaff, ariz. HIV positive since 1983 > Another Route to a Cure? // one step ahead of elite controllers: people who are immune to hiV infection.

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