THE VIRUS AT THE END OF THE WORLD
By Laurie Garrett
Esquire 1 March 1999
We thought the worst epidemic in history had been subdued. But this
is not the same AIDS. This is a monster that is mutating faster than we
can keep up. It's alive. It's healthy. And the worst is yet to come.
For the past several years, Spencer Cox, who is thirty years old,
has lived behind a dam built to contain the catastrophe that is the most
threatening virus of our time. It is a dam made of drugs designed to
keep him from dying of AIDS. Diagnosed at the age of nineteen, Cox, a
southerner who lives in Manhattan, became involved with the Treatment
Action Group, which put him in daily touch with the cutting edge of HIV
science. As each new drug was discovered, Cox was among those at the
front of the line to take it.
And he was among the first to unwittingly cultivate viruses that
were resistant, successively, to each of the new drugs he took. So for
the last two years, as most HIV patients have been gleefully grabbing
the latest combination therapies, Cox has already been experiencing
problems with them, as well as with just about every other anti-HIV
By late 1997, Cox's HIV-positive friends and fellow activists were,
for the most part, feeling the best they had in years. Some even looked
upon the gleaming dam and happily declared the end of AIDS. But Cox had
to concede that he had run out of options. Nothing worked against the
mutant microbes in his blood.
"None of us would say that having access to the best available
scientific information every step of the way has helped us
particularly," he says. "Professional judgment has consistently been way
out in front of evidence. We're going to have to rethink everybody."
When Cox says everybody, he means the two hundred thousand Americans
and at least an equal number of Western Europeans, Australians, and
Canadians who are living behind the dam with him. And the rest of the
33.4 million in the world who are desperate to get their hands on these
drugs. Treatments consist of more than 250 combinations of three or more
anti-HIV drugs that were first introduced in January 1996 and
popularized in the summer of that year. For the past two years, this dam
has blocked the mighty HIV river. But there are now grave problems.
"The worst-case scenario is that I'm back in 1987," Cox says,
referring to a time when there were no effective treatments for HIV. He
insists that he's always taken his medicines religiously, carefully, by
the book. And yet mutant viruses never fail to emerge eventually. As
this past Christmas approached, Cox anxiously studied his worsening test
results, praying that some new experimental treatment would be available
before HIV overwhelmed him completely.
Spencer Cox represents the future of this virus.
At the University of Alabama in Birmingham, Dr. Michael Saag
supervises research and the care of more than one thousand AIDS
patients. The treatment is positively state-of-the-art, often better.
Drug companies eagerly offer their newest innovations to Saag for
As physicians venture into ever wilder frontiers of HIV treatment,
the grand experiment with combination therapies, called Highly Active
Anti-Retroviral Therapy, or HAART, is rushing forward without any data.
No one is keeping track. Indeed, as a result of the "AIDS is over"
rhetoric, many AIDS service organizations have seen donations drop. So
they've cut back on their policy and research staffs. And all over
America, acute-AIDS-care facilities have shut down, breaking up teams of
scientists, physicians, and nurses that used to monitor patient outcomes
on a scale that offered vital information.
Saag's is one of the few remaining facilities, and his latest
results are not good. Talk of a cure is over. "Perhaps the biggest
difference between the cure paradigm and whatever paradigm we're in now
is, we now should expect failure with whatever [HAART cocktail] we first
use. We should plan on it. We should prepare for it. Clinicians should
Far from imagining patients feeling triumphant while their viruses
disappear, Saag sees a world in which "patients are only on regimens for
three to four months before they switch," either because resistance
emerges or side effects become unbearable. In one year, 157 of Saag's
patients collectively took 189 different drug formulas, with only three
patients taking the same mix of HAART drugs.
And despite such rigorous, individualized medical attention, Saag
says, the HAART dam "is already leaking, and there's high danger of it
collapsing altogether. There's no question that we're in a honeymoon
right now. Failures are occurring right and left."
The very first person treated with HAART was Saag's patient. In
August 1993, a young Alabamian started taking a drug called indinavir in
combination with two older anti-HIV drugs. The patient experienced a
miraculous recovery. By every measure, Saag says, he appeared to have
been "cured." But in early 1994, his viral load started to crawl back
up; the HIV became resistant to indinavir. For nearly four years, with
careful switching of his HAART treatment, the man survived.
"He died last April," Saag says with a heavy voice. "It tells me
that when people begin to fail virologically, they will eventually do so
clinically." By the end of 1998, Saag's massive data pool was
yielding alarming numbers. He could see that May 1997 had been the nadir
for AIDS deaths in his population. Since that time, death rates have
clearly been on the rise. "They aren't dying of a traditionally defined
AIDS illness," Saag says. "I don't know what they're dying of, but they
are dying. They're just wasting and dying.
"It is sobering," he continues. "While we are making good guesses,
they are just guesses. We don't know what we are doing. Hubris! Hubris!
We need to be scientists every step of the way and do our darndest to
seek what reality is."
Reality is that by their very nature, viruses, and particularly HIV,
have the better of human beings. Though this century has witnessed the
development of successful vaccines against such viruses as smallpox and
polio, and a handful of antiviral drugs have been invented, the course
of viral infection is usually determined by one thing: the human immune
system. And as the body musters its forces, viruses continually and
rapidly mutate. The greater the pace of this viral transformation, the
more difficult the immune system's work. It would take a revolution in
scientific thought to come up with a drug that would shift the odds in
favor of humans against the deadly elite of the viruses.
Every revolution has its Paul Revere, who shouts the news that
rallies despairing masses. For HIV, it was Emilio Emini, of the Merck
Research Laboratories in West Point, Pennsylvania. On January 29, 1996,
Emini stepped to the podium in an enormous hall in Washington, D.C., a
hall overflowing with thousands of scientists and physicians attending
the annual Conference on Retroviruses and Opportunistic Infections. He
summarized several small clinical studies conducted on fifteen patients
here, four there, another dozen over there. He was describing the
effects of then-unlicensed protease-inhibitor cocktails on people with
As Emini's slides, depicting plummeting HIV levels in the blood of
patients taking the novel cocktails, flashed before the gathering, the
excitement was unmistakable. And the audience went electric when Emini
described one of Michael Saag's patients who, after taking the Merck
protease inhibitor indinavir in combination with the older drugs AZT and
ddI, had had no detectable HIV in his blood for nearly two years.
"If this can be achieved with one patient, there is no reason to
believe it can't be achieved for many more patients," Emini told the
crowd. He was struggling to stifle a grin. "And what we're facing here
is a paradigm shift in the goals of HIV therapy. The goal now should be
to lower the viral load as much as possible, for as long as possible, in
as many patients as possible."
The usually staid scientists in attendance were beside themselves
with enthusiasm. So was Wall Street, which within an hour had pushed
Merck stock to a fifty-two-week high, gaining more than a dollar a
It's a home run, declared the ecstatic scientists.
But the greatest elation was felt among HIV patients and their
physicians. In San Francisco and New York City, where large numbers of
doctors handle HIV patients exclusively, the medical community eagerly
prescribed the new cocktails. By the summer of 1996, word of miraculous
deathbed recoveries had spread worldwide, and at the International
Conference on AIDS, convened in Vancouver that August, mountains of
evidence supported Emini's battle cry.
Word from Vancouver was simple and upbeat: New tests allowed
physicians to measure, with exquisite specificity, how many HIVs were in
a droplet of an individual's blood. The number of viruses, or the viral
load, correlated well with the patient's prognosis; high viral
loads--more than ten thousand HIVs per milliliter of blood--spelled very
bad news. But numerous studies showed that the new HAART cocktails
enabled the body to slaughter HIVs by the billions, bringing viral loads
down to below the limits of technological detection, which at the time
was about five hundred HIVs per milliliter.
Using even more-sophisticated technology, clinical researchers such
as New York's Dr. David Ho, Alabama's Dr. Saag, and Emini showed that
"zero detectable" HIVs in blood actually equaled no viruses in the
bloodstream. And on the eve of the Vancouver meeting, a small group of
top HIV researchers from all over the world gathered to cautiously
discuss one word: eradication. They dared not say "cure"--that word was
far too emotionally charged. But the group thought that powerful HAART
cocktails might actually eradicate all vestiges of HIV from an
And that--whatever one called it--would free the individual to go
off the drugs and live a full life.
By the time thousands of scientists and clinicians gathered in
Vancouver, Ho, Tufts University's John Coffin, and the University of
Alabama's Dr. George Shaw had calculated that every day, an untreated
individual's body made about ten billion viruses and a hundred million
new immune-system CD4 lymphocytes to battle them. Over the course of the
disease, this daily standoff shifted in HIV's favor, CD4 levels fell to
zero, and viral loads soared to upwards of half a million HIVs per
droplet of blood.
But in the presence of HAART, new HIVs were produced much more
slowly, proponents said, and the immune system had a chance to recover.
Eventually, the only remaining HIVs would be sequestered in hiding
places throughout the body, and after three to five years, they
predicted, those lethal reservoirs would die out.
Thus, they said, it might be possible to put thousands of people on
HAART for just a few years, watch HIV disappear, and then withdraw the
drugs. Voila. Eradication. An epidemic that by the close of last year
would claim 13.9 million lives--and imperil more than 30 million
Eradication. For the fifteen years of the epidemic before the
emergence of these drugs, hope was unknown for someone diagnosed with
AIDS. So a little excitement was understandable. And suddenly, the
science of AIDS itself seemed to mutate--from a science of inevitable
loss into something very different. It was a science of hope.
Propelled by the jubilant Vancouver news, tens of thousands of
Europeans and North Americans started taking HAART. And when the
international AIDS community reconvened last year in Geneva, results,
overall, still looked great. For example, in 1996, the number of people
in New York City who died of AIDS fell to five thousand, down from a
1994 total of nearly seven thousand. And rough data for 1998 shows about
thirty-five hundred deaths recorded. Similar trends have been seen in
most major U.S. cities. And nationally, AIDS death rates between 1996
and 1997 fell a breathtaking 47 percent.
Owing to the fact that there are forty-three million uninsured
Americans whereas Western Europe has near-universal health care,
Europeans have seen an even more dramatic trend. Between 1994 and 1998,
death rates for HIV patients fell an astonishing 80 percent. The
successes in Europe may also be a result of greater initial conservatism
there in the use of experimental anti-HIV drugs during the 1980-95
period, which could explain the lower rates of multidrug resistance seen
in European HIV patients.
But something was happening. HIV was not being eradicated. It would
hide. It would mutate. It would, it seemed, wait for the toxicity of the
new drugs to make its host sick in some other way. Wait for the sick
person to quit the drugs or reduce them or take them in some slightly
different way. And then it would come back.
Now, while drug companies tout genuine improvements in HAART--new
drug combinations that are easier to take and perhaps somewhat more
potent--they concede that earlier optimism about knocking out unique HIV
actions, such as integration of the virus's genes into human DNA, is
"I think we're probably as far away from cures as we are from
vaccines," says Peter Young, vice-president of HIV therapeutic
developments for the Glaxo Wellcome pharmaceutical corporation. In this
epidemic, we have historically witnessed peaks and troughs of research
optimism. Young acknowledges that the peaks felt last year are now
disappearing. "The image that comes to mind is a lot of people filling
The declining efficacy of HAART drugs is, Emini now says, "a
stochastic event. It's a matter of chance" that cannot currently be
predicted in any individual patient. "There are patients who, even
though they have suppressed the virus for years, will fail," Emini says
with deep regret in his voice. "So what does that tell you? It tells you
it's not an easy consideration to 'cure' a patient even after a long
time of suppression. The virus will cycle up."
HAART didn't lose its luster suddenly. Rather, it's been fading
slowly--so slowly, in fact, that it's easy for the denial-inclined to
ignore the new reality.
Last year, Dr. Neal Nathanson became head of the National Institutes
of Health's Office of AIDS Research, overseeing an annual scientific
budget of $ 1.7 billion. "My sense is that it won't be possible to keep
someone on HAART for a lifetime," Nathanson says. "Every death that
didn't occur last year is not a cure; it's just a postponed death. I
don't hear much optimism. I'm afraid that the death rate may start to
climb back up. The decline in mortality could be used to argue that we
should cut back in our research. And that would be disastrous."
Disastrous, Nathanson says, because there will soon be a need for
fundamentally new treatment strategies for AIDS. Most of the drugs now
in development at the approximately twenty-five companies targeting the
$ 5 billion U. S. HIV market, though, are simply variations on the HAART
theme. No viable drug that combats HIV in an entirely new way, and no
vaccine, is likely to find its way to the marketplace before 2005 at the
earliest. Even the rosiest forecast fails to envision a genuine HIV
vaccine in widespread use before 2015.
Meanwhile, for more than 95 percent of the 33.4 million people
living today with the disease, the $ 10,000 to $ 60,000 annual HAART
price tag is utterly out of reach. Per-capita health-care spending
averages ten dollars a year in each of Africa's hardest-hit
countries--nations in which 20 to 26 per cent of all men and women aged
fifteen to forty-nine years are HIV-positive.
Many researchers--including those originators of the eradication
hypothesis of 1996--now say that the reservoir of hidden HIVs in
apparently successful HAART patients is large and long-living. David Ho,
who was a pioneer of the combination therapies, now thinks patients
would have to take the difficult drugs for twenty-five to thirty years
to eliminate those hidden viruses. Some other scientists put the figure
even further out, at forty to fifty years.
It doesn't really matter, because either number is impossible. The
HAART drugs are difficult to take and increasingly are seen to cause a
range of nasty side effects. Chief among them is a mysterious change in
lipid metabolism that results in redistribution of body fat and elevated
cholesterol counts. The extent of the lipid problem in HAART users, and
the reasons for it, remain matters of vigorous debate. But there can be
no doubt of the disorder's severity when thirty-year-old men develop
cholesterol counts above 400, soaring triglyceride levels, skinny limbs,
and protruding paunches. The effect on women's bodies is even more
profound, as they develop large, waistless trunks and sticklike limbs.
So dramatic is the physical change that some people elect to discontinue
HAART and face death rather than spend longer lives in unrecognizable
bodies. After a year on HAART, some patients have their parents'
physiques. Or their grandparents'.
Many respond by dieting, taking hormones, working out at the gym.
But this is not the sort of problem that readily responds to such
effort. And no one in the field thinks cholesterol counts of 300 to 900
can be tolerated for long, even by a strong, youthful heart.
Anybody who takes ten to twenty even mildly toxic drugs a day is
giving his liver, kidneys, intestinal tract, and bowels a real beating.
Over time, these vital organs become less able to absorb and process the
medicines, so the antiviral agents never get to their targets. Some
HAART drugs cause damage to the nervous system. There are reports of
drug-induced hearing loss. And while such acute side effects appear in
less than 10 percent of all patients who stay on HAART for one to two
years, it is widely assumed that toxicity will increase over time,
simply because analogous approaches to treatment, such as those used to
fight cancer or drug-resistant bacteria, become increasingly toxic the
longer they are employed.
And the drugs are very difficult both to prescribe and to take. Some
can't be taken together; some exacerbate the effects of others; some
enhance others; and certain cocktails simply don't work well.
For patients, HAART can become a full-time lob. Some drugs must be
taken four times a day, some once, some twice. Some must be taken on a
full stomach, others before eating. And all well-managed HIV patients
also take a host of prophylactic drugs that prevent common opportunistic
infections such as parasitic pneumonia, a blindness-inducing virus, and
a bacteria similar to tuberculosis that's normally found in birds. It is
not uncommon for an HIV patient to be taking some type of pill every
Keeping track of all those pills, injections, salves, and the long
list of herbs popular in the HIV community is a daunting task. And
failure either to prescribe correctly or to follow doctor's orders
precisely promotes the emergence of drug-resistant viruses. In many
cases, the ever-mutating HIV is capable of making changes that allow it
to resist not just one drug but an entire class of them.
HIV develops resistance to antiviral drugs roughly the same way
bacteria become resistant to antibiotics, but HIV does it with a
frequency that is orders of magnitude faster than that seen with
bacteria. Any use followed by interruption and then reuse of the same
drugs gives HIV the opportunity to mutate and clone an enormous colony
of resistant viruses. And in the case of HAART, very brief
interruptions--on the order of days--are enough to shift the advantage
to the deadly viruses.
Companies have responded by developing quick resistance tests that
physicians can perform routinely on virus samples from their patients.
If a patient is found, for example, to have HIVs that have mutated to be
resistant to indinavir, the physician might then switch the client to a
cocktail that has a different protease inhibitor.
Unless, or until, the virus is resistant to all protease
No other disease, either infectious or chronic, is treated for years
on end with so complex a drug regimen. And the first drugs you take are
probably the most important, because everything you do after that is
going to be less effective.
There are no HAART cookbooks, and experts differ on every
fundamental aspect of standards of care: When should patients begin
HAART? With which combinations should they start? When the first round
fails, what second-line cocktails should be used? Every leading HIV
organization and national medical-research institute in the United
States and Europe has tried to answer these questions. They have all
reached the same conclusion: Answers must be found by each physician in
consultation with each patient.
In other words, because each individual case is an experiment, the
physician and patient must approach treatment choices in collaboration,
acting as a unit that embodies the traditional experimental research
team of guinea pig, scientist, doctor, and ethics review panel.
It's tailor-made medicine, surfacing at a time when managed-care
companies think that any general physician can handle HIV treatment. A
national HIV-treatment survey conducted last year by the University of
California San Francisco found that one out of four HIV patients was
receiving incorrect, out-of-date drug treatments for his infection. The
survey, which polled 476 American physicians, found that doctors who had
in their careers handled fewer than 100 HIV patients were the most
likely to prescribe the wrong combinations and to delay treatment until
their patients were too sick.
One way to get around this--decreasing both toxicity and
complexity--would be to simplify the regimens of HAART. Much hope was
placed on the possibility that a full HAART cocktail would be needed
only for a few months: Once the patient's viral load dropped to below
detectable levels, the patient could switch to an easier, two-drug
therapy. Large studies employing this strategy were conducted in Europe
and the United States. The grim results were published last October in
The New England Journal of Medicine. Patients who went on the simple
therapy were six times more likely to suffer dangerous viral rebounds
after six months than patients who remained on the more complex standard
treatment. No one can safely diminish the drug cocktail.
In fact, some physicians are moving radically in the other
direction, giving patients extraordinarily complex regimens. Manhattan
HIV specialist Dr. Howard Grossman determined that several of the drugs
used in HAART were prompting cross-resistance against other drugs, and
he was beginning to see an alarming number of failures among his
"So I talked about it, thinking, Should we add in other combinations
and recycle back in some old [anti-HIV] nucleosides?" Grossman says. The
result: Twice a day, Grossman's patients now take two protease
inhibitors, three nucleoside-class anti-HIV drugs, including a new
anti-HIV drug called abacavir, an old drug used for cancer care called
hydroxyurea, a nonnucleoside HIV blocker, and another new anti-HIV drug
called efavirenz. That's eight anti-HIV drugs, in addition to a plethora
of medicines aimed at preventing opportunistic infections, plus growth
hormone and testosterone to combat HIV-induced wasting. "And it's really
well tolerated," Grossman says. "It's amazing."
This "mega-HAART," as Grossman calls it, is now being taken by at
least forty patients, all of whom were failing standard treatment due to
the emergence of drug-resistant HIVs. Half have kept their viral loads
down to below the limits of detection, Grossman says.
Of course, every single one of them is suffering lipid-metabolism
side effects, and Grossman says he is "worried about the cardiovascular
stuff. Are we going to have ten thousand people who are having
myocardial infarctions before age forty?"
The data has caught up with "cure" and "eradication": Both concepts
are, for now, dead. The new vogue is "remission," a term taken from
another currently dismal field of medicine, cancer care. HAART, it is
argued, pushes patients into a remission in which the virus is forced
into hiding. The strategy then is to use HAART simply to bring viral
loads way down, then hit patients with something that packs a wallop to
their immune systems--often an agent that the body mistakes for an
infection--forcing cells that are harboring hidden HIVs to wake up,
release the viruses into the bloodstream, and thereby expose the
microbes to HAART drugs. There's no easy way to do this. Provoking the
immune system with such force makes people feel, at best, as if they
have the flu. With stronger hits, patients must be hospitalized in an
intensive-care unit during treatment.
Radical as it may sound, the approach has been tried in several
places, yielding mixed results to date. Dr. Joep Lange at the University
of Amsterdam put three patients through ICU care after placing them on a
five-drug HAART regimen. One of the patients left the hospital free,
according to tests, of any HIV. He pronounced himself cured and
disappeared, lost since to Lange's team. Other scientific groups have
had similar experiences, finding that a single patient here or there
seems to experience a remission that is roughly equivalent to going
cancer-free after chemotherapy. Of course, no responsible oncologist
tells such a patient that he or she has been cured of cancer.
The most positive remission results so far have been obtained at the
National Institute of Allergy and Infectious Diseases in Bethesda,
Maryland. There, director Dr. Anthony Fauci and his colleague Dr. H.
Clifford Lane have used a powerful human-immune-system stimulant called
interleukin-2, or IL-2, on fourteen HAART patients. The patients got
infusions of the chemical for five days at a time every eight weeks for
at least a year.
Most of the patients didn't get much more out of the IL-2 experiment
than several rounds of feeling as if they had lousy cases of the flu.
But six patients have had bona fide remissions. Fauci's group has found
no HIV in their blood--in more than 330 million cells analyzed per
person or in biopsied lymph nodes.
But what does this mean? Putting aside the astronomical costs and
practical difficulties of conducting the same treatment on a million HIV
patients in North America and Europe, does it work? Fauci is cautious.
He avoids using many words--not only cure and eradication, but also
Dr. Robert Siliciano at the Johns Hopkins School of Medicine in
Baltimore uses a new technology for searching for evidence of HIV in
seemingly "cured" patients, and his findings consistently point to
continued presence of HIV hidden deep in reservoirs in the body.
Siliciano searches for the presence of HIV genetic material integrated
into the chromosomes of human cells. These seemingly innocuous chunks of
DNA can, when stimulated, commandeer the genetic machinery and make
millions of copies of themselves that are released into the bloodstream
the moment HAART drug levels, for any reason, fall.
In Chicago, Dr. Steven Wolinsky of Northwestern University employs
similar techniques to search for HIV genes in seemingly effectively
treated patients. His new findings also suggest that viruses in these
patients are actively reproducing and, worse yet, mutating. Wolinsky
conducts painstaking DNA and RNA analysis of HIV samples drawn from
several HAART patients at various points over the years they are on the
therapy. He uses an ultrasensitive assay first to look for whole viruses
in the patients' blood. Then he looks for pieces of viral genes.
He consistently finds that certain HIV genes are being produced even
when a patient's viral load is below zero for more than a year. And one
key viral gene, called nef, never goes away, even when all else
disappears. In every case, nef levels begin to increase in the patients
about six months to a year before the rest of the viral markers rise and
well before a clinician would recognize that treatment was failing.
"After eighteen months on therapy, the patient's back to where he
started. And that's the reality," Wolinsky says. "The virus is not
gone--it's still there years out. So the question is, is this an
evolutionary question? Is there ongoing replication?
"Why do we always see nef RNA? The virus is telling me something,
but I'm not smart enough to see it," Wolinsky says with a shrug. "Is the
sky falling? I wish I knew."
HIV is made up of many genes; nef is perhaps the most tantalizing
but least well understood. A few years ago, Ronald Desrosiers of
Harvard's New England Primate Center caused tremendous excitement when
he demonstrated that monkeys vaccinated with a live, genetically altered
AIDS virus that had no nef were immunized against all subsequent
exposures to the virus. It looked as though Desrosiers had found the
Holy Grail: an AIDS vaccine. But later it was shown that baby monkeys
and chimps and mice did get AIDS when vaccinated with nef-deleted
viruses--it just took longer. How and why have not been discerned.
Nef-deleted viruses appear to stay in latency. And nef-active viruses,
Wolinsky believes, eventually cycle up in HAART patients.
Mario Stevenson of the University of Massachusetts Medical Center in
Worcester is one of the world's experts on nef. He says the mysterious
gene "is mind-boggling to scientists," who simply cannot agree about its
role in the course of disease events.
"It's like mud just now," Stevenson says. "Many of the things we
know about the virus just don't make sense."
Stevenson sees nef and other HIV genes in successfully treated HAART
patients, too. And he thinks that HIV is always reproducing and
changing, despite the seemingly effective therapy. Merck's Emilio Emini
says that there is "no doubt about it at all," that HIV replicates and
mutates in seemingly effectively treated patients. But he thinks more
research will be needed to see whether Wolinsky's nef hunch is true.
But that, in the end, isn't nearly as important clinically as the
overall consensus now reached among scientists: HIV will reproduce and
mutate. Period. Unless fundamental breakthroughs are made in anti-HIV
science, the miracle of 1996 is finished.
Denial and fear of facing failure can be seen among scientists, says
Steven Wolinsky. "I don't understand where all this optimism comes from.
The problem is hope-driven science. The problem is reading your data
through a prism of hope, rather than seeing it for what it is."
"We've said from the beginning, this is a nasty little virus," says
Emini. "My fundamental hope is that in the end we'll be able to make a
sincere shot at a vaccine here."
A shifting emphasis to a vaccine, of course, means giving up on the
33.4 million infected. Burnout and death have decimated the ranks of
traditional AIDS activists. Those who remain recognize that HAART isn't
the answer, and they rage over the medical community's tendency to blame
the patients for somehow creating their poor fates by failing to adhere
to their drug schedules. They claim that the biomedical community feels
no urgency in the matter and isn't searching for radically new drugs.
Since 1994, Dave Gilden has edited Treatment Issues, published by Gay
Men's Health Crisis in New York. He's been organizing new protests aimed
at the drug companies. "Look, the drugs are getting more expensive, half
the people in the U.S. aren't getting any, all those people in Africa
are getting written off, and there's no attempt to find simpler, more
effective treatments," Gilden says.
And most problematic, activists feel that their own HIV communities
cast vitriol against them for speaking about the truly dire state of
Well-known New York activist Michelangelo Signorile says that a sort
of mass denial has set in. "People were furious that I would be saying
that AIDS did not go away. I've been accused of causing panic, being
hysterical. People are embarrassed to talk about the fact that the drugs
aren't working for them, and even to say that their lover recently died
of AIDS--because of that sense of failure." So strong has been the
attack on Signorile that he is giving up and moving to New Zealand.
Another loud voice, Gabriel Rotello, author of Sexual Ecology, has
opted for the "calmer" world of network television production.
There's another small problem. New HIV infections have continued to
mount, but often in different social groups than before. While new
infection rates appear to have declined among gay white men in North
America, for example, they have risen steadily elsewhere. A striking
illustration of the change can be seen in the Bay Area, where until the
early 1990s, by far the majority of all new HIV infections occurred
among gay white men living in four key neighborhoods of San Francisco.
By last year, the new-infection rate in that group, and in the city
overall, had fallen.
But across the bay in Alameda County, officials declared a crisis in
late 1998, when number crunching revealed that 41 percent of all newly
diagnosed HIV cases were African-Americans, although blacks make up just
18 percent of the county's population.
Further surveys published since November of last year reveal that
far more than half of all people infected with HIV in America do not
receive HAART drugs, primarily because they are outside the circles of
sophisticated HIV care. In fact, the Rand group has concluded--after
surveying thousands of health--care providers and HIV patients--that
fewer than a third of those infected have the sort of private insurance
that would allow access to specialized HIV treatment; about one in every
five of them has no health insurance at all, and the remainder are on
Medicare or Medicaid. A substantial majority of uninsured and Medicaid
patients are African-American or Hispanic.
Estimates are that approximately 200,000 Americans are being treated
with HAART drugs today, although somewhere between 650,000 and 900,000
Americans have been infected with the virus, according to the U.S.
Centers for Disease Control and Prevention. Health analyst Derek Link of
GMHC estimates that there are 50,000 people in New York State alone who
should be in treatment but are not, either because they lack access to
appropriate health care or--as is especially common in the communities
now being hardest hit--because they are unaware of their HIV status. Dr.
Perry Smith of the New York State Department of Health thinks that's a
reasonable guess, adding that his office "gets about 51,000 undiagnosed
as an upper limit" on the number of New Yorkers who are unaware that
they are HIV-positive. Dr. Helene Gayle of the CDC says, "Our estimates
are that a third of the people who are HIV-positive don't know it."
Given that most experts on combination therapies advocate use of the
drugs soon after infection, this seems to indicate an enormous gap
between the number of Americans who ought to be on HAART versus the
roughly one third of those infected who actually are, and who already
shoulder what experts estimate was in 1998 a $ 5 billion national bill
for anti-HIV medicines.
All over America, state and federal health officials are planning
big campaigns for 1999 aimed at encouraging people to get tested for HIV
and, if positive, to get on HAART.
Which could be a mighty hard sell, given the mounting evidence that
these therapies ultimately will not work.
What exactly lies in the months ahead? Overall, the experts say, it
appears that in the absence of an unexpected breakthrough, most, if not
all, HAART patients will eventually run out of treatment options. They
will then be in Spencer Cox's position--in limbo, waiting and hoping for
a new drug.
Given that most of the two hundred thousand or more Americans
currently on HAART started taking the drugs during the last quarter of
1996, the bulk of that population will likely reach the limits of their
therapy at about the same time. Already, more than a third of all
patients who started the drugs during the exciting days of 1996 have
failed on the therapy. And for those still sitting comfortably behind
the dam, the reservoir is increasingly turbulent, filled with bodies
that are rebelling against drug toxicity or being overwhelmed by viruses
that are evolving to outwit the HAART cocktails.
If Dr. Saag in Birmingham is correct and the first cracks have
already appeared in the HAART dam, 1999 could be the Year of Great
Disappointment as clinic after clinic across America finds itself trying
to cope once again with acute AIDS cases. It will pose remarkable
challenges, as few cities still have centers of excellence for AIDS
care. Further, the demographics of the HIV population have shifted
radically since the American epidemic's mortality peaks in 1994. But it
will be worse this time: More and more, HIV hits the country's most
alienated sectors. These are people who lack the resources and skills to
demand proper treatment. The fastest-growing group is African-American
women, most of whom acquire the virus through heterosexual contact. Many
are impoverished mothers. The new HIV population doesn't have the same
organization and political clout that successfully confronted three
presidents, Capitol Hill, the world's largest pharmaceutical
conglomerates, and the scientific research establishment during the
period between 1984 and 1994.
They are less like Howard Grossman's gay white clientele. And more
like Dr. Wafaa El-Sadr's Harlem Hospital patients.
"Fifty-three percent of my patients fail therapy by twenty-four
weeks," El-Sadr told the twelve thousand scientists at last summer's
international AIDS conference in Geneva. Lester, a reformed IV-drug
user, is typical, she said. After complaining about how much he needs to
read in order to decide what to do about his HIV, Lester simply asked,
"Should I take these drugs?"
"We don't know," El-Sadr said. "Will these drug regimens work? How
can I answer?"
All anyone can do is look at the numbers, chart the graphs, map the
projections: The trajectory doesn't look good. With time notched out in
weeks, extending from July 1996 through the end of 2000, and graphed
against numbers of HAART patients whose treatments are failing, it takes
a heap of denial to reach anything but sobering, even grim, conclusions.
And time, once again, is the enemy, for it favors the virus. In the
time it has taken you to read this article, millions of new HIVs were
made in the body of a typical unmedicated patient, thousands in a HAART
patient. Some of the viruses will have developed capacities that they
didn't have when you began reading.
Minute by minute, HIV gains advantage. Our best defense against it
is slowly giving way. And it will take a lot more hard work, money, and
creative human thinking to come up with a way to shore up the dam--or
build a better one.
After doing graduate work in immunology at UC Berkeley, Laurie
Garrett decided to become a journalist. Today, not only is she the
medical and science writer for New York Newsday, but she is the only
writer ever to win the top three prizes in her field: the Pulitzer, the
Polk, and the Peabody. Garrett has been covering AIDS since 1981, in the
days before the scourge had a name, so this month's cover story, "The
Virus at the End of the World" (page 102), was a long time coming.
"We're currently in an acute optimism phase in which the public, most
HIV patients, government agencies, and the majority of HIV caregivers
feel that genuine advances have been made that have all but eliminated
AIDS," says Garrett, author of The Coming Plague (available in paperback
from Penguin) and The Death of Health (to be published this year by
Hyperion). "But this optimism doesn't jibe with what I feel the
scientific data supports. And unless some serious scientific
breakthroughs are made swiftly, we'll all be hurting terribly in the