Time - Man of the Year/Time_Man_of_the_Year_Compact_Publishing_3YX-Disc-1_Compact_Publishing_1993.iso/moy/080392/08039926.000

Text File | 1993-04-08 | 18KB | 373 lines

                                                                                COVER STORIES, Page 30

INVINCIBLE AIDS


By CHRISTINE GORMAN -- With reporting by Dick Thompson/Amsterdam


    Strange new cases that do not seem to be caused by the known
HIV viruses. Drug treatments that no longer look so promising.
New complications in the search for a vaccine. Suddenly, the
AIDS outlook has become bleaker: more heterosexual transmission,
more cases among women and a rising death toll well into the
next century.


    Wars are usually launched with the promise of a quick
victory, with trumpets primed never to sound retreat. And the
campaign against AIDS was no exception. Soon after researchers
announced in the mid-1980s that they had discovered the virus
that causes AIDS, U.S. health officials confidently crowed that
a vaccine would be ready in two years. The most frightening
scourge of the late 20th century would succumb to a swift
counterattack of human ingenuity and high technology.

    But no one was making any victory speeches last week in
Amsterdam, where more than 11,000 scientists and other experts
gathered for the Eighth International AIDS Conference. The mood
was somber, reflecting a decade of frustration, failure and
mounting tragedy. After billions of dollars of scattershot
albeit intensive research and halfhearted prevention efforts,
humanity may not be any closer to conquering AIDS than when the
quest began.

    There is no vaccine, no cure and not even an indisputably
effective treatment. While AIDS education has slowed the
epidemic in developed countries, the disease continues to spread
rapidly in many poorer nations. The World Health Organization
says at least 30 million people around the world could be
infected with the AIDS virus by the year 2000. Other experts
think the number could reach 110 million.

    Despite dogged detective work by the world's best
researchers, AIDS (acquired immunodeficiency syndrome) remains
one of the most mysterious maladies ever to confront medical
science. The more researchers learn about the disease, the more
questions they have. Human immunodeficiency virus (HIV),
proclaimed to be the cause of AIDS, has proved to be a
fiendishly fast-moving target, able to mutate its structure to
elude detection, drugs and vaccines. No one knows for sure how
HIV destroys the human immune system, and puzzled experts have
debated whether the virus is the only culprit at work.

    Bewilderment reached a new level in Amsterdam, where
scientists reported cases of people who have an AIDS-like
condition but have not been found to be infected with HIV. That
frightening revelation raised the possibility that a new AIDS
virus is emerging. Another theory, suggested by France's Dr. Luc
Montagnier, who first discovered HIV, is that the strange cases
were caused by one or more mutant forms of HIV that were altered
too radically to be detected by standard blood tests.

    Hardly any of the news at the conference was good. As
groups of protesters staged daily demonstrations demanding more
action against the epidemic, Dr. Jonas Salk suggested that
vaccine researchers were on the wrong track, and the actress
Elizabeth Taylor blasted President Bush for not doing enough
about AIDS. Delegates heard reports on the surging costs of
treatment, warnings about the threat of AIDS-associated
infections such as multidrug-resistant tuberculosis, and
alarming projections that AIDS will become more of a
heterosexual disease. The infection rate among women is rising
and will pass the rate in men by the year 2000.

    "We're dealing with something that's expanding out of
control," said Dr. June Osborn, chair of America's National
Commission on AIDS. Dr. Anthony Fauci, director of the U.S.
National Institute of Allergy and Infectious Diseases, noted
that "the science is going as fast as it has with any disease,"
but he admitted that "the advances over the last several years
are clouded and dwarfed by the size of the growing epidemic."
Mark Harrington, a member of the New York City-based Treatment
Action Group, summed up the situation more simply and grimly:
"It's clear we're losing the battle. We have one class of drugs
that slows AIDS down by two or three years, and then people go
on and die."


    THE MYSTERY OF NON-HIV CASES

    The biggest surprise in Amsterdam was the talk about a new
kind of AIDS. Dr. Jeffrey Laurence of the New York
Hospital-Cornell Medical Center described five instances of
people who suffer from an AIDS-like illness and yet bear no
trace of HIV anywhere in their body. When a similar case was
reported at last year's AIDS conference in Florence, it was
dismissed as a fluke. This year several scientists in the
audience stood up to tell of other cases of non-HIV AIDS,
bringing the total to about 30 -- a number that is small but
impossible to ignore.

    Is a deadly new microbe on the loose? Speaking in the U.S.
last week, Dr. Sudhir Gupta of the University of California at
Irvine claimed to have found one in patients with AIDS-like
symptoms. But there is no proof yet that the virus caused the
symptoms. It is possible that the patients don't have AIDS but
have some other problem with their immune system that mimics the
disease. "It's just very premature to talk, because we don't
know if it's real," says Fauci. "We should know something in a
matter of months."

    Even if there turns out to be a new virus, people should
have no reason to panic or refuse blood transfusions.
Researchers think they can isolate the pathogen within months
and develop a blood test. In the meantime, this unusual type of
AIDS, whatever causes it, is very rare. Said Laurence: "Every
major AIDS researcher is here in one place in one room, and
still we're talking about only a handful of cases."

    The bad news, if a new virus does exist, is that AIDS will
become even harder to prevent or cure. Pharmaceutical
manufacturers have already been hampered by HIV's talent as a
quick-change artist. Only last year a group of promising
anti-AIDS drugs had to be shelved because HIV adapted too easily
to the medication. And drugs that prove effective against all
forms of HIV will not necessarily knock out an entirely novel
virus.

    HIV is a formidable enough opponent, mainly because
researchers still don't understand the method to its madness.
Like all viruses, HIV is simply a strand of genetic material (in
this case the nucleic acid RNA) surrounded by a protein coat.
A virus lacks the tools to reproduce unless it invades a living
cell and takes over the host's molecular machinery. The intruder
can then produce many copies of itself, eventually killing the
cell. One of HIV's favorite targets is the CD4 T-cell, an
important player in the human immune system.

    But there the understanding runs out. Why does HIV lie
dormant in human cells, usually for years, before producing a
full-blown case of AIDS? What triggers the deadly phase of the
infection? How does the virus go about destroying the immune
system? Even at the height of the disease, HIV particles are
found in no more than 1 in 100 CD4 T-cells. And yet the cells
that do not harbor the virus die off almost as fast as those
that do. Some researchers think that HIV must somehow provoke
immune-system cells to destroy themselves.

    One prominent theory is that the virus needs an assistant
assailant -- a "co-factor," in scientific jargon. But the search
for co-factors has been inconclusive. Although the presence of
genital sores from syphilis or other venereal diseases makes
transmission of the AIDS virus easier, neither the sores nor the
microbes that cause them are necessary for HIV to spread.
Researchers have also investigated the possibility that
cytomegalovirus, a common form of herpes virus, might be the
elusive co-factor, but eventually they ruled it out. "It has to
be something that's not too obvious," says Dr. Kent Sepkowitz
at the New York Hospital-Cornell University Medical Center.
"Otherwise, we would have figured it out a long time ago."

    Montagnier believes that the co-factor might be a
mycoplasma -- a primitive bacterium-like organism. The possible
role played by this microbe may help explain one of the
mysteries surrounding the origin of AIDS. Studies of blood
samples preserved from decades ago show that HIV was present in
Africa long before AIDS appeared. What caused the once harmless
virus to turn deadly? Monta gnier thinks it was a strain of
mycoplasma that until recent years was confined to America.
Somehow, somewhere, according to his theory, HIV and the
mycoplasma got together in a group of humans, and that was the
start of the AIDS epidemic.


    POWERLESS DRUGS, ELUSIVE VACCINES

    If HIV were an ordinary virus, designing drugs to kill it
might not seem like an impossible mission. "But it is a much
more difficult virus than anyone anticipated," says Myron
Essex, head of the Harvard AIDS Institute. "It has many more
fancy genes to determine how it replicates. It has positive and
negative controls that interact with cellular controls, which
allows it to crank up rapidly or remain silent for a long time.
It's a very, very unusual virus."

    Most important, HIV can easily disguise itself by altering
the proteins in its outer coat. When that happens, the job of
finding and attacking the virus becomes harder. Even AZT, the
most effective drug against HIV, is nowhere near as potent as
doctors or patients hoped it would be.

    First approved for use in the U.S. five years ago, AZT
prevents one of the viral genes from making an enzyme, called
reverse transcriptase, that is critical to HIV's reproduction.
This action prolongs life by postponing some of the symptoms of
AIDS. But in patient after patient, HIV eventually mutates into
a form that is less vulnerable to AZT. As a result, the drug's
benefits generally run out within 18 months.

    The only other anti-HIV drugs approved in the U.S. -- DDI
and DDC -- are variations on the AZT theme. Researchers have
begun examining other types, however. One variety targets the
gene that codes for another enzyme, protease, that is crucial
to the manufacturing of viral proteins. The research looks
promising, but a breakthrough is not expected anytime soon.

    The same adaptability that makes HIV so troublesome to
drug designers threatens to stymie vaccine development as well.
Researchers are not at all confident that they can devise a
simple series of shots that would give a person lifetime
protection against AIDS. To do that, a vaccine would have to
ward off all of HIV's current strains as well as any future
mutants.

    Neutralizing HIV is especially tough because its coat is
laced with sugar molecules that shield it from the human immune
system. Some viruses, such as the one that causes polio, have
no sugar in their protein coat. Others, like flu viruses, have
only a little. It is no coincidence that the most effective
vaccines have been made to fight these kinds of viruses. Never
before have scientists tried to devise a vaccine against a
pathogen as well protected as HIV.

    Undaunted, researchers are testing about a dozen
experimental vaccines. After the trials have been thoroughly
evaluated, the most promising prototypes will be chosen --
probably in the next two years -- for testing to determine if
they can stimulate the immune system to produce antibodies
capable of blocking HIV infection. The trouble is that
scientists can only guess at what constitutes an effective
collection of AIDS antibodies. No one has ever survived the
disease to provide researchers with any clues. Even if the
experiments go well, a preventive vaccine will probably not be
available before the end of this century.

    In the meantime, Dr. Robert Redfield of the Walter Reed
Army Institute of Research in Washington and his colleagues are
trying to develop a vaccine that helps people who are already
infected. By injecting a slightly modified form of the virus'
protein coat, the Army researchers hope to kick-start the
patients' immune systems into mounting an effective
counterattack. Redfield thinks that his version of the viral
coat may share enough characteristics with all the known mutant
strains of HIV to overcome the variability problem. Said
Redfield, a rare, unabashed optimist at the Amsterdam meeting:
"I believe HIV is very simple, very straightforward, and it's
going to be solved."


    THE EVOLVING EPIDEMIC

    One of the most baffling enigmas of AIDS is the fact that
the disease spread primarily among homosexual and bisexual men
and intravenous drug abusers in the U.S. and Europe but became
a largely heterosexual infection in Africa. Researchers
announced last week that they may have an answer. Based on a
study of the newly emerging epidemic in Thailand, they concluded
that HIV has shown predilections for different human host cells
in different parts of the world.

    Using biochemical tools that were not available at the
beginning of the epidemics in Africa and the Americas, molecular
biologist Chin-Yih Ou and his colleagues at the U.S. Centers for
Disease Control found two distinct epidemics caused by somewhat
different strains of HIV in the northern Thai city of Chiang
Mai. Both epidemics started no more than four years ago, but one
occurred mostly in intravenous drug abusers and the other
started in female prostitutes. There was little overlap between
the two groups.

    The scientists discovered that the prostitutes were more
often infected by a strain resembling those types found in
Africa. Apparently, it preferred the moist mucosal tissue of the
genital organs, making heterosexual transmission easier. The
other variety, found in the drug abusers, appeared similar to
strains detected in the U.S. and Europe. It thrived on immune
cells in the bloodstream. As a result, transmission occurred
through the exchange of contaminated blood, as might occur
during the sharing of needles or in abrasive anal sex.

    The rise of two or more dissimilar types of HIV could
explain why AIDS did not explode among heterosexuals in the U.S.
and Europe, yet spread rapidly among men and women in Africa
and parts of Asia. HIV has still not evolved in the
industrialized world into a form that is easily transmitted by
heterosexual activity. But it probably will, given the virus'
proven ability to mutate. "Over time, in the U.S., more and more
strains will adapt to become more efficient at heterosexual
transmission," Essex says. "So far, there haven't been a
critical number of people infected heterosexually. As that
happens, you will get adaptation of the virus for transmission
in that route. The heterosexual epidemic in the U.S. will
expand."

    Already American physicians are seeing more women with
HIV. In many AIDS clinics in San Francisco and New York City,
women make up 30% to 50% of all new patients. About half of them
became infected through heterosexual contact. They range from
very well educated to barely literate, but most of them say
they had no idea that their sexual partners had engaged in
high-risk behavior. In fact, because AIDS is still thought of
as a gay man's disease in the U.S., many women discover that
they are infected only after they have passed the virus on to
their children.

    Another alarming trend is that more and more AIDS patients
are developing tuberculosis. Normally, they respond to the
traditional treatments for this degenerative lung disorder.
However, a growing number of AIDS patients are contracting a
much deadlier form of TB that is resistant to standard drug
therapy. In Amsterdam Dr. James Curran, head of the AIDS program
at the CDC, called the combination a "double epidemic."

    Since the bacteria that cause TB spread through the air,
they threaten not only AIDS patients but healthy people as
well. Those with an intact immune system can usually fight off
the infection, but this does not hold true for people who
harbor HIV. Until the resurgence of TB, medical personnel who
were HIV-positive but still healthy could work on AIDS floors
without jeopardizing their own or anyone else's well-being. Now
they will face a greater risk of encountering and developing
TB. More AIDS patients are thus likely to be treated under
quarantine conditions to avoid spreading the TB bacteria.

    Tragically, even as AIDS goes in ever more dangerous
demographic directions, government agencies throughout the world
are failing to respond. Prevention programs are stalled or being
abandoned. The World Health Organization's AIDS budget for this
year is $90 million, down from $110 million two years ago. In
the U.S., the National Institutes of Health requested $1.2
billion for AIDS in next year's budget, but President Bush
trimmed that amount to $873 million and Congress is likely to
cut it even further.

    By the year 2000 AIDS could become the largest epidemic of
the century, eclipsing the influenza scourge of 1918. That
disaster killed 20 million people, or 1% of the world's
population -- more than twice the number of soldiers who died
in World War I. "This epidemic is of historic scale," says June
Osborn of the U.S. AIDS commission, "but the response has been
far short of historic."