HIV Negative - "Noble Doctors Try New Drugs on AIDS Orphans"

by Liam Scheff

Crux Magazine. November, 2004.

http://www.cruxmag.com/asset/crux_hivnegative.pdf



In June, 2003, I got a call to investigate a place called
Incarnation's
Children Center (ICC), a Catholic orphanage for HIV-positive children
in New
York City. I was told that terrible things were happening there.



ICC is a home for children who test HIV-positive. Some of the children
are
orphans; their parents use drugs and can't care for them. Some of the
children have parents and families, but the parents have trouble
enforcing
the heavy AIDS drug regimen. When that happens, the city agencies bring
the
children into ICC, where their drug regimens are carried out without
fail.



Their press page describes ICC as an "Ellis Island . . . envisioned as
a
sanctuary of love, a home-like nurturing residence where HIV-positive
children would receive the best possible nursing and medical care while
awaiting placement into foster homes."



That didn't sound so terrible.



ICC was also receiving federal funds for running drug trials with the
children. "In 1992, an outpatient clinic for HIV-positive children was
established; the same year, with funding from the National Institute of
Allergy and Infectious Diseases [a subdivision of the NIH], the clinic
became a sub unit of the Columbia University Pediatric AIDS Clinical
Trials
Unit." In 1996, "under the direction of Dr. Stephen Nicholas,
thirty-four
children [were] participating in seven clinical trials . . . ."



Dr. Nicholas was listed among "The Best Doctors in New York in New York
Magazine and in the 1996-97 edition of The Best Doctors in America."
ICC
received government trial-funding through 2002. Dr. Nicholas has since
moved
to Harlem Hospital. ICC's new medical director is Katherine Painter.
She
told me that children at ICC are now enrolled in clinical trials at one
of a
dozen area hospitals that work in conjunction with ICC. "Children
participating in a drug trial undergo monitoring, testing, and supply
of an
experimental drug through their outpatient clinic, and we maintain that
treatment here," she said.



If I wrote for the New York Times, I would have had my story: "Noble
Doctors
Try New Drugs on AIDS Orphans."



On the surface, it sounds innocuous and slightly tragic, but also
heroic and
perhaps hopeful. New drugs-that can't be a bad thing, can it? AIDS
orphans.
Well, if anyone deserves a new drug, it's AIDS orphans, right?



But I had doubts and lingering questions. What exactly are the "new
drugs?"
Do they have any effects that are deleterious? The ICC webpage listed
them.
It turned out that the drugs weren't really new at all-they were
old-nearly
40 years old. The primary drug used in trials at Incarnation Children's
Center is called AZT. It was developed in 1964. So, not a new drug.
Does
that matter? No, if the drug helps the kids. But there was a problem.



AZT isn't a very helpful drug-unless, I suppose, you enjoy funerals.
AZT has
a very special use. It's a chemotherapy drug used to kill the cells
that
make up living tissue and blood. It was designed in a cancer research
lab in
1964 as a potent cell-killing agent called a nucleoside analogue. It
works
by disrupting cellular replication at the genetic level.



Our DNA is made up of four bases that combine in pairs. These line up,
spiraling into a double helix. DNA codes for all our proteins; it's a
blueprint for our building blocks. AZT stops the spiral; it breaks the
chain
and kills the cell. Not so innocuous, after all.



AZT never got out of the lab. It was far too effective at killing cells
even
for short-term use. It was shelved, and no patent was filed.



In 1986, Burroughs Wellcome (now GlaxoSmithKline) was interested in
entering
the AIDS drug market. Recycling an old drug was cheaper than designing
a new
one. So AZT was brought out of storage. Test labs that ordered the drug
for
experimentation received it in a package bearing a skull and crossbones
on a
bright orange background. The label read "TOXIC. Toxic by inhalation in
contact with skin and if swallowed. Target organ(s): Blood bone marrow.
If
you feel unwell, seek medical advice (show the label where possible).
Wear
suitable protective clothing."



Today, Glaxo sells AZT under the brand name "Retrovir" and as an
ingredient
in  "Combivir" and "Trizivir." But the warning label tells the same
story:
"Retrovir [AZT] has been associated with Hematologic Toxicity [blood
toxicity], including Neutropenia [loss of neurophils, an essential
component
of blood] and Severe Anemia [potentially fatal lack of blood
production] . .
. Prolonged use of Retrovir has been associated with Symptomatic
Myopathy
[muscle wasting]."



"LacticAcidosis and Severe Hepatomegaly [liver swelling] with Steatosis
[fat
degeneration], including Fatal Cases, have been reported with the use
of
Nucleoside Analogues [AZT, 3TC, ddl, D4T] alone or in combination,
including
Retrovir and other Antiretrovirals (see warnings)."



The most surprising thing about AZT is that it doesn't even claim to
work:
"Retrovir is not a cure for HIV infection . . . The long-term effects
of
Retrovir are unknown at this time . . . The long-term consequences of
in
utero and infant exposure to Retrovir are unknown, including the
possible
risk of cancer."



This wasn't so wonderful for the kids at ICC. But it was good for
Glaxo.
They make a lot of money with their AIDS drugs. Drugs containing AZT as
an
ingredient account for about one billion British pounds (over 1. 5
billion
dollars) in Glaxo's 2002 sales alone. Other nucleoside analogues
provide
another 470 million pounds (750 million dollars) in sales.



We know that something doesn't have to be good for you to be
profitable.
Think of cigarettes or alcohol or fast-food. But it's medication we're
talking about, not French fries. You'd think that a drug with such
terrible
toxicities would simply never get approved for use by the US Food and
Drug
Administration (FDA).



Unless, of course, the FDA approval process was easily corrupted. For
example, a bad drug might get approval if a trial were heavily
influenced,
and even overseen, by the very pharmaceutical companies that produced
the
drug. That would mean that pharmaceutical reps, with a vested interest
in
getting the drug to market, would oversee and direct the recording
process
during the drug trial-or perhaps that CEOs of drug companies would go
work
at the FDA for a stint, approving drugs, then turn around and get back
into
the company.



Or perhaps doctors would be given favors-I don't know, expensive trips,
monetary rewards, that sort of thing-to be loyal to a particular
product, or
to review it favorably. Or that doctors fell victim to peer pressure
from
inside their academic community to support an ongoing paradigm, and not
to
rat out a bad public health policy.



But even suggesting that sort of thing is ridiculous, isn't it?  I
mean,
there's no corruption in pharmaceutical-driven medicine. Is there?



Here's a hint.



In 2000, Dr. Marcia Angell, editor of the New England Journal of
Medicine
(NEJM), resigned from the journal. In her parting May 2000 editorial,
"Is
Academic Medicine for Sale?" Angell wrote, "[Y]oung physicians learn
that
for every problem, there is a pill (and a drug company representative
to
explain it). [Physicians] become accustomed to receiving gifts and
favors
from an industry that uses these courtesies to influence their
continuing
education . . ."

She added, "[T]he costs of the industry-sponsored trips, meals, gifts,
conferences, and symposiums and the honorariums, consulting fees, and
research grants are simply added to the prices of drugs and devices."



Angell asked, "What is the justification for this large-scale breaching
of
the boundaries between academic medicine and for-profit industry?"



ABC News reported that in 2000 pharmaceutical companies sponsored over
314,000 promotional events for doctors-from lunches to travel
weekends-at a
cost of nearly 2 billion dollars.



In 2002, the new editor of the NEJM, Dr. Jeffrey Drazen, officially
dropped
the journal's 190-year restriction against medical authors accepting
money
from drug companies. The journal's editors claimed that there simply
weren't
enough doctors who didn't have ties to drug company money. The new
policy
allows review authors to accept up to 10,000 dollars a year from each
drug
company for "speaking and consulting fees"-with no limit on total
earnings.
By contrast, there are no financial restrictions placed on the
researchers
running the studies, who often work directly for the company whose drug
is
being tested.



Does money influence drug studies? ABC News reported that in a survey
of
independently-run drug studies, drugs were found to be safe and
effective
about 50% of the time. But when a drug company sponsored their own
trial,
the positive rating nearly doubled to 90%.



Even without evidence of corruption, FDA approval does not ensure drug
safety. According to the US General Accounting Office, 51.5% of drugs
approved by the FDA from 1976 to 1985 had "serious post-approval
risks,"
including "heart failure, myocardial infarction, anaphylaxis,
respiratory
depression and arrest, seizures, kidney and liver failure, severe blood
disorders, birth defects and fetal toxicity, and blindness."



In 1986, AZT was rushed through its FDA approval trials in record
speed.
Overseen and funded by Burroughs Wellcome, the trials were marred by
false
reporting and a total breakdown of study controls. Nevertheless, the
drug
was released to the market.



Subsequent independent AZT studies revealed the obvious-the drug was
deadly.
In English, Australian, and Dutch studies, patients on AZT developed
severe
anemia, requiring multiple blood transfusions just to stay alive. In
the
Dutch study, three-quarters of the patients on AZT died.



Well, AZT wasn't the only drug being used at ICC. The other was
Nevirapine,
which is marketed under the brand name "Viramune." And that drug . . .
maybe
we shouldn't talk about that drug. Oh.might as well.





Nevirapine functions similarly to AZT. It interferes with the essential
movement of genetic information in the cell. It blocks an enzyme which
translates RNA into DNA.



There was a short period in research biology where it was imagined that
this
enzyme, called Reverse Transcriptase, only functioned in service to a
particular kind of potential virus. This was quickly proven false. The
enzyme didn't belong to any particular virus or molecule. It was a part
of
normal, healthy cells-essential to our functioning. And Nevirapine
blocks
it.



Is that a bad thing? It is for people who've taken it whose skin has
come
off of their bodies. Right, well, I didn't quite believe it myself,
until I
saw the European study of Nevirapine. Hands, abdomens, faces, and
mouths,
bursting with blood, flesh coming off like old paint steamed off a
wall. The
condition is called Stevens-Johnson Syndrome. Of course, those patients
could have saved themselves the pain and just read the drug label (if
they'd
only been shown it). Here's what it says:



"Severe, life-threatening skin reactions, including fatal cases, have
occurred in patients    treated with Viramune [Nevirapine]. These have
included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis,
and
hypersensitivity reactions characterized by rash, constitutional
findings,
and organ dysfunction. Patients developing signs or symptoms of severe
skin
reactions or hypersensitivity reactions must discontinue Viramune as
soon as
possible."



It also warns of liver failure/toxicity. It seems that the drug can
toxify
the liver to such a great extent that it, well, dies: "Severe,
life-threatening and in some cases fatal hepatoxicity [liver damage],
including hepatic necrosis [liver death] and hepatic failure, has been
reported in patients treated with Viramune."



The other drugs used in the children's regimen are called protease
inhibitors. They have warning labels of their own, and they're pretty
painful too. Not much better, maybe worse. Doesn't seem like much of a
favor
to these orphans. But these drugs-AZT and Nevirapine, protease
inhibitors-aren't just used on orphans in NYC. These are the main AIDS
drugs
used on people who doctors consider at risk for AIDS all over the
world.



There's been time to measure the effect of AZT. It has been given to
hundreds of thousands of gay men in the US who tested HIV-positive,
whether
they were sick or not. United States AIDS deaths increased by thousands
annually after the mass-introduction of AZT in 1987, from 11,000 in
1986 to
nearly 50,000 in 1994-the height of AZT use. Sharp criticism of AZT
began
appearing in the press. Patients and physicians complained openly of
the
drug's effects and cut doses or discontinued it altogether. The death
rate
declined-substantially-and before the introduction of protease
inhibitors,
which the industry likes to credit for the decline. Was it a
coincidence? I
don't know. You can't ask dead people what they died of. I do think
it's
worth looking into.



So why were infants at ICC getting AZT? Weren't there better solutions?
ICC
seemed to think so. From their published history: "Early in the
epidemic,
HIV disease of childhood was considered to be a down-hill course
leading to
death. But in the late 1980's, before AZT was available, many very ill
children admitted to ICC got dramatically better with proper nurturing
and
high-quality medical and nursing care."



Why didn't they stick with this program? Was it the government funding?
Was
it political pressure to get the drug approved for new markets? It
certainly
wasn't the effectiveness of the drug. We don't hear stories in the
current
AZT/Nevirapine era about "many very ill children" becoming
"dramatically
better."



So, there were problems at ICC. But they certainly couldn't force the
children to take the drugs, could they?



Well, actually, they could. And they do.



How do they do it? It's not pleasant to tell. Maybe you don't want to
know.
Anyway, if it's not in the New York Times, maybe it's not important.
But I
had to ask.



I talked to  ICC's medical director Dr. Katherine Painter about it. She
kindly provided details of the surgery given to children who "can't
take" or
simply refuse the drugs. As per medical protocol, these children have a
tube
surgically implanted in their abdomens through which the drugs are
easily
administered, regardless of the child's wishes. I wrote about it in an
article called "The House That AIDS Built" and in a second article
called
"Orphans On Trial," which was published in the New York Press in July,
2004.



I haven't seen anything on it in the NY Times. But, of course, the
chief
writer on HIV at the NY Times is (and has been for over 20 years) a man
named Lawrence Altman. And Lawrence Altman can't write stuff like this,
even
if he wants to.



You see, Altman is a former graduate of the CDC-the organization that
makes
the rules for how HIV patients are treated and diagnosed in this
country.
So, of course, Altman's hands are tied. "All the News That's Fit to
Print"
suddenly has a very clear, very unpleasant meaning.



Next time you see the headline "New AIDS Drugs for Africa" or "Noble
Doctors
Try New Drugs on Orphans," what will you think? Will you ask yourself
what's
behind it? If you want to find out, you'll have to dig a little.



References and Further Reading:

"Orphans On Trial."  Liam Scheff.  New York Press; July 14, 2004.

"Is Academic Medicine For Sale?" Dr. Marcia Angell. New England Journal
of
Medicine; May 18, 2000.

"Big Pharma, Bad Science." Nathan Newman. The Nation; July 25, 2002.

"Death by Medicine." Gary Null PhD, Carolyn Dean MD ND,  et al. 
Nutrition
Institute of America. November,    2003.

"Conflict of Interest?" John McKenzie. ABC News; June 12, 2002.

"AIDS; Words From The Front." Bryan Ellison. Spin. December, 1993.