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
"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
"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
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
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."