HAS AIDS BEEN BEATEN?
By Colman Jones
Now On 2-8 Jan. 1997
Four months ago, Michael Steeler was a very sick man. He and his
doctor both thought the end was near.
"I had bargained on it," Steeler tells me. "I had geared
my finances and everything else to dying within the year."
Before his AIDS diagnosis in 1990, Steeler had led a distinguished career
as a banker, ship broker and publisher of trade magazines. After years
of trying almost every experimental treatment that came along, he was losing
weight fast and his body was overtaken by chronic diarrhea.
Then, in an eerie scenario now being replayed throughout North America
and Europe, Steeler began taking one of the newly available pharmaceutical
compounds recently licensed to fight HIV. His symptoms quickly disappeared
and he began gaining weight, yet another tentative success story in what
may prove to be the most dramatic treatment advance so far in this public
Just when it was beginning to look like the struggle to come up with
a useful AIDS treatment was going nowhere, a new sense of hope emerged.
Although no one is quite prepared to trot out the "C" word just
yet, all eyes are focused on this latest class of AIDS treatments, known
as protease inhibitors.
But the science of how to use these new remedies is foggy. And there
is a disturbing subtext - the consensus as to which drugs to take and,
more importantly, when to take them is being developed under the watchful
eye of an industry intent on marketing them to as many people as possible.
This state of affairs has led to concerns about the reliability of the
information - supplied mostly from drug company presentations - people
are relying on to make critical treatment decisions.
In July, a panel of top AIDS researchers issued a series of recommendations
in the Journal Of The American Medical Association (JAMA). They advised
people with HIV to take these new, relatively untested therapies even if
they're not sick but simply show a certain amount of the virus in their
blood, opening the door to a much larger pharmaceutical market than just
full-blown AIDS cases.
The move may well be justified, but some are beginning to question the
motives behind the recommendations, given the backgrounds of the 13 panelists.
In accordance with recently developed rules of disclosure, JAMA published
an addendum listing the authors' ties to industry. All but one had received
financial support from AIDS drug makers, it turns out. Two of the panelists
actually own stock in companies producing anti-HIV compounds such as protease
inhibitors, JAMA says.
At medical meetings, the constant presence of pharmaceutical reps is
causing unease for some participants, who worry about perceived - or real
- conflicts of interest in a potential multibillion-dollar market.
Should those who stand to profit from this biotechnology bonanza be
the same people who are entrusted to impartially review the scientific
evidence and issue recommendations?
Such issues matter little to Steeler. For him and others with HIV, the
motives of the drug researchers matter less than the drugs themselves and
their potential to offer him and others like him a new lease on life.
The latest addition to the AIDS treatment arsenal, protease inhibitors
are designed to attack HIV by blocking an enzyme said to be crucial to
the virus' reproduction, thereby crippling its ability to make more copies
of itself - at least in theory. Accordingly, using several antiviral treatments
in combination offers more opportunities to attack the virus.
Preliminary results indicate that using one or more of these drugs,
often in combination with older AIDS drugs, causes levels of HIV in the
blood to shoot down dramatically and the number of infection-fighting white
blood cells to rise. Some unpublished studies even hint that patients taking
these new formulas may actually be living longer - a first in more than
a decade of AIDS drug development.
Indeed, if their effect on HIV levels in the blood is any indication,
the drugs deliver a whopping one-two punch. In one study of indinavir,
marketed by Merck-Frost under the trade name Crixivan, more than a third
of those taking the drug had virus levels either at or well below the detectable
limits of the currently used tests. This measurement of viral load, as
it's known, is overtaking the counting of immune system cells as the chief
"surrogate marker" doctors use to tell whether an anti-HIV treatment
For some observers, however, decreases in viral load have to be placed
in perspective. "All of the drugs - AZT, etcetera - lower viral load,
even down to undetectable levels," says Billi Goldberg, a prominent
community treatment activist from San Francisco who insists the latest
therapies are worthless.
While there is genuine uncertainty over the exact significance of these
viral load tests, improvements in the immune systems of people taking these
drugs are held up as further evidence of their benefit. The main yardstick
of immune function most experts have traditionally relied upon is the number
of white blood cells, known as CD4 cells, per cubic millimetre of blood.
(Healthy people generally have between 800 and 1,000 CD4s, whereas people
with HIV are currently defined as having AIDS if they show fewer than 200.)
In the indinavir study, patients on the drug showed an average increase
of more than 100 CD4 cells after six months, in many cases a doubling of
As with blood virus levels, however, numbers of CD4 cells alone are
not the be-all and end-all of immune well-being.
This was perhaps most conclusively demonstrated by the British-French
Concorde trial, the largest and longest of its kind, comparing HIV-positive
people taking AZT earlier and later in infection. It found that those who
began taking the drug early on consistently showed higher CD4 counts yet
died just as quickly as those who waited until they got sick, clouding
the precise relationship of CD4 counts to improved health.
Furthermore, despite increases in CD4 cells, their ability to fight
infection is not necessarily improved. A group of Dutch researchers found
that "Although treatment with a protease inhibitor resulted in the
most persistent elevation of both CD4 and CD8 T-cell counts, T-cell functional
improvement was of limited duration."
The ultimate test of any AIDS therapy takes place in the clinical setting,
where both doctors and patients are primarily interested in preventing
illness and death. In this respect, the reports flooding in about health
improvements are the kind doctors and patients could only dream of even
as recently as a year ago.
Says Joseph Sonnabend, a long-time AIDS physician in New York, "This
is the very first time in the history of this disease that I see people
who come back a month later - and the month after that - and they're better
than they were. You don't know what that feels like - it's just terrific."
As a result, word is spreading like wildfire about these new therapies,
and patients are storming into doctors' offices demanding them. Maurice
Genereux, a Toronto HIV primary care physician, says he's been deluged
by requests for prescriptions in the last six months.
Interestingly, many AIDS doctors don't feel the same enthusiasm as their
patients about protease inhibitors, according to a Hoffmann-La Roche survey
of 409 participants in a recent protease inhibitor symposium. Some physicians
interviewed for this article express a cautious optimism about the efficacy
of the drugs and are waiting to see more information on their toxicity
and impact on survival.
Philip Berger, chief of the department of family and community medicine
at the Wellesley hospital, agrees it's too soon to tell what the impact
of these therapies is going to be.
"Do they do something? Yes, they do. Have I seen spectacular recoveries
on the drugs? Absolutely. In everybody? No. In some people? Yes, and it
is absolutely amazing. How long is it going to last for? I don't know -
that's all I can say."
Sonnabend is quick to caution that "The protease inhibitors are
not performing as their strongest adherents would have you believe. The
clinical benefits have only been demonstrated in people who are rather
sick. Most people don't benefit, because it doesn't work or they can't
tolerate it, and in the people for whom it works, it stops working for
At the core of the current uncertainty over the new compounds is the
fact that no one knows exactly how best to administer them, or to whom.
"Even if the promise of some of the combinations that we're seeing
lasts for a long time, there are still a lot of people for whom that's
not the answer, whose access to these treatments may be difficult or whose
immune systems have already suffered too much damage," adds Glen Brown,
director of programs and services at the Canadian AIDS Treatment Information
There's also the question of side effects and interactions with the
other medications patients may be taking. Of particular concern is ritonavir,
one of the most highly touted of the new products.
"There are a whole slew of other drugs that you can't take with
ritonavir," notes CATIE treatment service coordinator Craig McClure,
"because of the way the drug is metabolized in the body."
In fact, 17 per cent of the volunteers in a ritonavir trial conducted
by the manufacturer, Abbott Laboratories, had to give up treatment because
of adverse side effects.
As a result, AIDS treatment activists are hesitant to overly laud these
"Protease inhibitors are perhaps the beginning of the search for
an end," says McClure, "in the sense that they are helping people
to live longer and healthier, but they're not in any way, shape or form
Amidst all this contradictory information, people living with HIV are
left with few places to turn for accurate, unbiased information about their
One school of thought holds that treatment should be started as early
as possible to prevent damage to the immune system.
"These drugs should be available to everyone no matter what the
CD4 count is, early on if they choose," Genereux says. "I don't
think there should be limits - set by anyone - on who has access to the
Others, like New York's Sonnabend, are more cautious, warning that not
enough is known about the long-term effects of protease inhibitors.
"They're doing the same thing as with AZT," Sonnabend points
out. "People who are not sick - asymptomatic people - are being placed
on these drugs, with no evidence whatsoever that they're going to be helped
by them. And those people may actually be hurt because of long-term toxicity."
The uncertainty as to when to begin treatment is reflected in the differing
criteria being issued, on the one hand, by researchers and, on the other,
by provincial governments - who have to pay for these latest additions
to the AIDS treatment arsenal.
For example, it was recommended at the Vancouver AIDS conference that
anyone with a viral load higher than 5,000 copies per millilitre of blood
should be taking anti-HIV drugs, regardless of their CD4 cell count. Yet
in Ontario, the new treatments are only available to people already taking
anti-HIV therapy who have fewer than 500 CD4 cells, whether or not they
have a high viral load.
Exactly who should have access to the protease inhibitors is no trivial
matter to a province concerned with cutting costs. The new drugs are pricey
- a months' supply of Saquinavir alone runs at $550.
While debate continues over when to begin prescribing the new drugs,
the definitive answer on whether they really stall AIDS can only be found
by conducting properly controlled clinical trials.
But there's a catch-22 here. Because new anti-HIV preparations are continually
being unveiled, organizing such trials is problematic owing to the reluctance
of patients to keep taking an "old" drug. Furthermore, because
of all the different concoctions of drugs being experimented with, trial
designers face a unique challenge in trying to allow participants a certain
degree of autonomy while still being able to achieve a meaningful scientific
What little evidence there is about an actual clinical benefit from
these new treatments has mostly taken the form of interim reports presented
by drug companies at medical conferences, not papers published in the peer-reviewed
Some are suspicious of this kind of preliminary information, pointing
out that it was the same sort of unpublished data that led to the 1990
licensing of AZT for HIV-positive people without symptoms, a move that
later trials like Concorde cast resounding doubts on.
In fact, that trial - the longest and largest of its kind - showed that
more people taking the drug early on died than those who waited until illness
Oddly enough, when the JAMA panelists reviewed AZT studies as part of
the July recommendations, neither the Concorde trial nor another critical
study from the U.S. Veterans Affairs Administration was even cited, leading
some to wonder how impartial these drug company-funded reviewers really
The omission of two key studies critical of early AZT use was pointed
out in a September report published in JAMA, penned by Berger, that drew
attention to the considerable ties between the panelists and industry.
Berger's concern about the increasingly blurry relationships between
leading researchers and AIDS drug manufacturers was highlighted at a conference
held last October in Toronto by the HIV Trials Network.
Funded by eight different AIDS pharmaceutical firms, it was convened
to develop prescription guidelines for AIDS treatment. Drug company sponsorship
of such events isn't that unusual, but some in attendance were struck by
the constant presence of company marketing reps, even in the small group
discussions hashing out recommendations on how and when to prescribe the
drugs - recommendations that will form the basis for HIV treatment in Canada
for years to come.
(Final recommendations on when treatment with these drugs should begin
are expected to be announced in the next couple of months.)
Brown, who attended the October conference, doesn't know whether or
not the guidelines were influenced by pharmaceutical reps in the room.
"I'm not entirely sure, but I feel fairly confident that the conversation
would have been just the same if they weren't in the room."
But untangling the complex web of ties between drug companies, researchers
and activists is no easy task, given all the interdependent relationships
that have developed in the course of the epidemic.
"If companies stop funding HIV research, then you'd never have
to worry about conflict of interest," says Pat Hanrahan, a spokesperson
for Hoffmann-LaRoche, maker of Saquinavir. "But you'd also never have
to worry about drug therapy, either," since drug companies provide
the bulk of research funding.
Don Zarowny of the Canadian HIV Trials Network, who organized the October
conference, agrees. "If we throw away all the researchers who receive
funding from the private sector, we'd have nobody left." He says declining
government funds means there's no choice but to have the pharmaceutical
industry finance such meetings.
Zarowny rejects notions that discussions about prescribing recommendations
were influenced by the presence of drug company representatives at the
"We aired this in a small group prior to the meeting, and the bottom
line was that there was no perceived threat from the presence of these
people. It would be very difficult to promote a drug that was ineffective
or extremely toxic."
Drug company hype is the last thing on Genereux's mind. "These
drugs market themselves. The results are so impressive that the clinicians
are trying to get these drugs before they're available."
But not all AIDS activists are impressed by this latest twist in the
search for AIDS treatments. Perhaps most radical in outlook is the San
Francisco chapter of the AIDS Coalition to Unleash Power (ACT UP), which
has clearly distanced itself from the other ACT UP groups with its ringing
denunciation of the antiviral approach to AIDS.
"AIDS research money is all being dumped onto the study of these
entirely worthless, highly toxic and extremely profitable pharmaceutical
treatments," says Todd Swindell, a spokesperson for the group. "Things
that will boost the immune system and alleviate the opportunistic infections
- those areas are not being looked at."
To most workers in the AIDS field, this small group of radical guerrilla
activists is merely taking advantage of paranoia fed by the disastrous
results of AZT. Brown calls them "sociopaths," at least those
he met in Vancouver.
Ultimately, the bottom line is the day-to-day health of people with
AIDS, like Steeler, whose seeming recovery is hard to argue with. Like
many people with AIDS, he is trying to come to grips with the prospect
of a life he thought he was leaving behind. Many of his friends are dead,
and he has no idea whether the benefits he's experienced will last indefinitely
or wear off.
"I am hoping, of course, to stay around long enough to find something
else that will help keep me going, until something else proves more effective,"
Steeler says. "Earlier this year, I had made my mind up that I would
be dead within a year, so every day is a new gift."