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Dr. Robert Gallo

The Virus Fighters
by Elizabeth Arledge

Since the discovery of the human immunodeficiency virus (HIV) in 1984, millions of dollars and thousands of hours of scientific effort by some of the best minds in the world have gone into trying to crack open its arsenal of secrets. AIDS today is considered a "treatable" disease for many patients in Western countries; combinations of powerful anti-viral drugs can stall the progress of HIV and keep these lucky patients healthy for many years. But for the vast majority of people infected, especially those in developing nations, these drugs are of no use. They are unavailable and too expensive, requiring life-long adherence to demanding dosage regimens, which are impossible in conditions of extreme poverty and limited medical care.

Therefore, basic scientific work on understanding the virus and a search for a vaccine that might replace these drugs goes on with a tremendous sense of urgency.

"There's been a shift in the research in a couple of ways," says Dr. Robert Gallo, director of the Institute of Human Virology at the University of Maryland and co-discoverer of HIV. "The early years were more about trying to find out and understand anything. Now, I think, most scientists doing laboratory research on HIV, the immune response, and the disease are more cognizant of thinking that the research should have some practical utility. People are giving more thought to biological approaches to control the disease, on manipulating the immune response, and, of course, on developing a preventive vaccine." (For an update on the hunt for a vaccine by Dr. David Baltimore, chairman of the National Institutes of Health's AIDS Vaccine Research Committee, see Search for a Vaccine.)

Gallo's lab is currently focusing intense attention on a group of naturally occurring chemicals in the immune system called chemokines. Chemokines are tiny molecules involved in signaling and communication among cells involved in immune response. One critical recent discovery has been that certain chemokines are able to block HIV infection.

"I don't think they were designed for that purpose," says Gallo. "It's a stroke of luck and a stroke of nature." In 1995, his team discovered that certain chemokines can physically block the receptor proteins on the surface of cells that HIV uses to infect them. Their quest now is to see if there may be a way to replicate this blockade in drug form. The hope is that a new class of drugs to intervene against HIV might prove successful with patients who cannot tolerate the current anti-viral "cocktails," or might offer a less expensive way to keep the virus at bay without years of ongoing treatment.

Dr. Norman Letvin

Many scientists, meanwhile, are turning their attention toward the idea of a "therapeutic" vaccine—one that would not prevent AIDS infection but would keep an infected individual from succumbing to the ravages of the disease. This new approach is partly the result of the realization after years of effort that a completely preventive vaccine for a virus as devious as HIV might prove impossible.

"Making a vaccine to prevent HIV infection is orders of magnitude more difficult than a vaccine to prevent other infectious diseases we've conquered in the past," says Dr. Norman Letvin of Beth Israel Deaconess Medical Center in Boston, who is a member of the National Institutes of Health's AIDS Vaccine Development Advisory Committee. "Other vaccines have been successful because they have not had to generate what we would call sterilizing or absolutely protective immunity."

A good example of a vaccine that doesn't actually prevent infection with the virus but keeps the individual from contracting disease is the polio vaccine, Letvin says. The polio virus enters the body and replicates initially in the blood. It eventually makes its way to the spinal cord, where it causes disease. "The polio vaccine doesn't prevent the polio virus from entering the blood," Letvin says. "Rather it slows down the replication of the virus just enough to prevent it from entering the spinal cord and causing neurologic disease."

Since HIV attacks immune cells, however, many researchers worry about allowing even a tiny amount of the virus to replicate in the blood. They believe that HIV's ability to linger and mutate in cells for many years would mean that it would eventually emerge and cause AIDS. Says Letvin: "What we are asking the HIV vaccine to do is to stop the virus cold."

Dr. Anthony Fauci

A vaccine that might lessen the severity of HIV infection and avoid the symptoms of AIDS is now at the forefront of research. Scientists are searching for ways to develop a vaccine that would not prevent HIV infection but rather would control the virus once it entered the body.

"I think we'll have a vaccine that will have a major impact on the epidemic in being able to slow the spread," says Dr. Anthony Fauci, head of the National Institute of Allergies and Infectious Diseases. "If you have a vaccine that keeps replication of the virus to such a low level that you have difficulty spreading it to another individual, then interruption of the acceleration of the epidemic is attainable."

Letvin concurs. "We must accept the fact that it may never be possible to attain true sterilizing immunity against HIV with a vaccine," he says. "What we may have to accept is a vaccine that can decrease the amount of viral replication, leading to a much longer period of clinical latency, a period of non-disease. Even such an imperfect vaccine would be of tremendous benefit in areas of the world where this virus is endemic and treatments are simply not available."

Dr. Bruce Walker

While a viable vaccine has thus far remained elusive, the work taking place in the search has led to numerous scientific breakthroughs. "Research that's been done on HIV has pushed science in multiple different directions," says Dr. Bruce Walker, director of AIDS research at Massachusetts General Hospital. "The molecular virology of HIV, the way in which the virus reproduces itself, the way in which the virus gains entry into cells—all of the discoveries that have been made related to HIV relate to other viruses as well. There are countless examples of investigators who started out working on HIV who have been able to apply the things they've learned in HIV to the study of other viruses."

Fauci agrees. "It's been an extraordinary catalyst in understanding things we never understood before," he says, then adds more soberly, "Right now the advances in HIV research are bringing us closer and closer in some cases to partial solutions, but in other cases to the realization of the formidable task we have ahead."

Elizabeth Arledge produced the NOVA program "Surviving AIDS."

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