 May 3, 2005The Inexplicable Survivors of a Widespread Epidemic
Nothing happened. It has been 16 years since Mr. Brothers learned he was H.I.V. positive. Since then, he has never taken AIDS drugs or had any illnesses associated with the disease. Despite his good fortune, Mr. Brothers says he feels isolated. "I don't identify with people who are H.I.V. negative because I'm not," he said. "I could infect someone. I don't identify with the positive people, because I don't have to deal with my health and medications and the things they have to worry about." Once a month Mr. Brothers visits the laboratory of Dr. Jay Levy, a professor at the University of California, San Francisco, who is director of the university's laboratory for tumor and AIDS virus research. Since the epidemic began in 1981, Dr. Levy has been trying to understand why Mr. Brothers and others who are H.I.V. positive can remain medicine-free yet fit for decades, while the average person with H.I.V. progresses to AIDS within 10 years, if untreated. An answer to that question could help in the development of a vaccine. As a long-term survivor, also known as a long-term nonprogressor, Mr. Brothers, 42, is a much sought after anomaly. Dr. Levy believes that about 5 percent of people with H.I.V. are medicine-free and still healthy after 10 years. Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases defines nonprogressors as treatment-free people with H.I.V. who have so little virus in their blood that it cannot be routinely detected. He suggests their numbers are far smaller, more like 0.2 to 0.4 percent. Whatever the percentage, locating these research subjects is challenging. In the early years, one of Dr. Levy's volunteers trolled gay bars looking for survivors. A number of Dr. Levy's volunteers take part in other studies, here and at the infectious diseases institute in Bethesda, Md. Long-term survivors have been around for a long time, said Dr. Mike McCune, senior investigator at the Gladstone Institute of Virology and Immunology. "We just don't know why they do what they do," Dr. McCune said. Martin Delaney, founder of Project Inform, an H.I.V. information and advocacy organization based in San Francisco, said: "The disappointing thing is that there's no consensus about what the long-term nonprogressors do. Different things explain it in different people." For many years, Mr. Brothers said, he carried a sense of guilt. Before his infection was discovered, his church encouraged him to donate blood four times a year. The blood bank discovered that one of its donors was H.I.V. positive and asked that Mr. Brothers, too, be tested. Reluctant to learn the truth, he refused and quit donating blood. In retrospect, Mr. Brothers, who had a flu-like illness in 1981, an early symptom of infection with the virus, believes he was H.I.V. positive before he began donating blood. "This is something I contributed to and could possibly have meant dozens of people contracting the virus and dying," he said in an interview. For years, he wanted to be part of a study. Five years ago, friends told him about Dr. Levy's research. Even when AIDS was a death sentence, Dr. Levy, a virologist, knew that every virus had its survivors. He believed he could learn from those whose bodies had kept the virus in check. Some of Dr. Levy's subjects have been H.I.V. positive for 27 years, longer than there has been an epidemic. The dates of infection were confirmed by the San Francisco Department of Public Health, which in 1978 began a hepatitis B study of 6,704 gay men, whose blood was preserved. Over time, some of these nonprogressors have turned into slow-progressors, dying of AIDS. But there remain a dozen who are infected but have stayed healthy for more than 20 years without treatment. In 1986, Dr. Levy discovered that in survivors, the white blood cells, known as CD8 cells secreted minuscule amounts of an antiviral factor that blocked replication of viruses in cells but did not kill them. The better the antiviral activity of those cells, the healthier the individual. Dr. Levy has devoted his career to trying to determine what that factor is. "It is the hardest thing I've ever had to do," he said. When Dr. David Ho, the founder of the Aaron Diamond AIDS Research Center, reported that he had found the substance, Dr. Levy told him he was mistaken. Repeatedly, Dr. Levy has told peers that they are wrong. He is also his own worst critic: "After a while they say 'Levy is spending all this time telling us what it isn't. What is it?' " he said. Over the years, Dr. Fauci said, many people have grown skeptical. "I have tried to find the factor, and I can't find what it is," Dr. Fauci said. "I can demonstrate the phenomenon, but I can't isolate the factor." Ten years ago, Dr. Robert C. Gallo, a co-discoverer of the AIDS virus and the director of the Institute of Human Virology and Division of Basic Science at the University of Maryland Biotechnology Institute, said he was "fed up" waiting for Dr. Levy to reveal the elusive substance. While searching for it, Dr. Gallo, along with Dr. Paolo Lusso, discovered three chemicals, called chemokines, in the blood of long-term nonprogressors that inhibit a certain subset of the virus, "like bouncers at a disco," Dr. Gallo said. He did not find Dr. Levy's mysterious factor. But Dr. Gallo's research has opened a new field of therapy. By 1996, when better treatment became available and people with H.I.V. were living longer, interest in survivors had diminished. But when it became apparent that a vaccine was still sorely needed, Dr. McCune said, the interest re-emerged. Many researchers have focused on the late stages of AIDS, but Dr. McCune compares that method to piecing together the fabric of an ancient civilization by examining its ruins. He and others are now focusing on H.I.V.'s early stages. By studying long-term nonprogressors, they are raising questions about what types of immune responses are useful against H.I.V. and about when, in the course of the disease, they can have an effect. "The main thing long-term nonprogressors teach us, and it keeps coming back again and again and again, is that it's not just the virus; it's the host," he said. Dr. Eric Rosenberg, an infectious disease doctor and assistant professor at Harvard who focuses on the earliest stages of infection, compares CD4 cells to generals in a bunker. In most people with H.I.V., he said, the generals quit ordering the CD8 "soldiers" cells to kill H.I.V.-infected cells. But in the nonprogressors, the CD4's continue to give their marching orders. Although many survivors attribute their good health to daily exercise, positive thinking, visualization or eating egg whites, Dr. Levy said it was all about genetics. When his subjects ask him why they're surviving so long, Dr. Levy said, he tells them, "You chose the right parents." Dr. Mark Connors of the infectious disease institute's Laboratory of Immunoregulation has enlisted 19 subjects from around the country. "Many of these folks are true altruists," he said. "These are very healthy people," yet they drop their careers to have blood examined at his laboratory. Robert, a computer programmer who stopped by Dr. Levy's laboratory to have his blood drawn, said, "I feel strongly about making a contribution as I pass through this life." Robert, who did not want his last name used out of privacy concerns, has been healthy and medicine-free for the 19 years he has been infected. Being in good health, after so many of his friends have died, seems somehow wrong. He harbors "this horrible secret," horrible, he said, because "I look healthy but I'm a carrier; you're carrying something that's fatal, but it's not fatal to you." Long-term nonprogressors "are telling us we're missing something big with regard to how immune system works," Dr. Connors said. Ninety-five percent of the long-term nonprogressors he studies share a gene that encodes molecules, allowing the immune system to recognize infected cells. Only 10 percent of progressors have that gene. While researchers ferret out more information, Mr. Brothers has changed his ways. He has developed a long-term relationship, bought a house and is adding to his 401(k). "I want to indulge in the future," he said. "I plan on being here for the long run." |
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