Government officials, AIDS organizations and the media unanimously
agree that the recent decline in AIDS cases and deaths is an unprecedented
occurrence due to a new combination of drugs that include protease
inhibitors, chemicals said to block the replication of HIV. However,
a careful look behind the headlines reveals that there is no medical
evidence to support these popular claims about the protease inhibitor
The declines in AIDS deaths attributed to combination therapies
actually began several years before protease inhibitor drugs became
available for general use. (72) Since the first protease inhibitor
received Food and Drug Administration (FDA) approval in December
of 1995, a more likely explanation for decreased deaths would be
the change in the official AIDS definition adopted in 1993 which
allows HIV positives with no symptoms or illness to be diagnosed
with AIDS. Since 1993, more than half of all newly diagnosed AIDS
cases are counted among people who are not sick. (73)
CDC data also show that decreases in AIDS cases commonly ascribed
to "AIDS cocktails" preceded the introduction of the new
drug treatments by three full years. According to the CDC's HIV/AIDS
Surveillance Report, AIDS diagnoses peaked in the third quarter
of 1991, increased once in the first quarter of 1993 as a result
of the 1993 expanded AIDS definition, and have dropped each year
News stories of AIDS patients who rise from their death beds to
run marathons after taking the drug cocktails, are just that --
stories. In science, such unverified accounts are dismissed as anecdotal,
a term that comes from the Greek word anekdotos, meaning unpublished.
None of the anecdotal tales of recoveries attributed to new drug
combinations have been substantiated by controlled studies published
in peer-reviewed medical journals, a fact acknowledged in the fine
print of pharmaceutical advertisements:
"At this time there is no evidence that Ziagen will help you
live longer or have fewer of the medical problems associated with
HIV or AIDS."
"It is not yet known whether Crixivan will extend your life
or reduce your chances of getting other illnesses associated with
"At present, there are no results from controlled clinical
trials evaluating the effects of Viramune [on] the incidence of
opportunistic infections or survival."
"There have been no clinical trials conducted with Combivir."
Incomplete and inconclusive data from one 1997 study are used to
claim that mortality rates are lower among HIV positives treated
with protease inhibitors. (77) This particular trial was prematurely
terminated before statistically significant results could be obtained,
and no placebo control comparing unmedicated HIV positives was used,
no recurrent AIDS-defining illnesses that appeared among participants
were recorded (except recurrent pneumonia), and the results mentioned
in the final report are for only a small fraction of the patients
enrolled in the study. (78) Current pharmaceutical ads use this
study to declare that their new drugs are "proven to help people
with HIV live longer, healthier lives" while simultaneously
admitting that "because the study ended early, there was insufficient
data to determine [the drug's] statistical impact on survival."
While there is no evidence that cocktail therapies produce clinical
health benefits, well-documented side effects include headache,
fever, nausea, vomiting, diarrhea, oral lesions, abdominal pain,
severe fatigue, sexual dysfunction, general ill feeling, skin rashes,
a hypersensitivity reaction that can result in sudden death, nervous
system damage, enlarged liver, liver failure, kidney stones, kidney
sludge, physical deformities including hunchbacks, sunken cheeks,
and "stick-like limbs," diabetes, heart disease, "unmasking"
of various opportunistic infections including CMV retinitis (a viral
infection which can lead to blindness), and spontaneous bleeding
in hemophiliacs. (80)
Media reports attributing declines in AIDS to protease inhibitor
cocktails often neglect to mention the high rate of drug failure
or the considerable number of HIV positives who either quit the
new combinations because of intolerable side effects or have never
taken them at all. Recent studies place drug failure rates at 50%
while others note that as many as 40% of participants drop out of
protease inhibitor drug trials due to adverse effects, and as AIDS
expert Dr. James Curran laments, "fewer than 10% of US AIDS
patients have access to and are on the new wonder drugs." (81)
For more information on the chemotherapy/protease inhibitor drug
combinations known as HAART, please see A Sobering Report on AIDS
Cocktails and What's Up with Viral Load? on pages 32 and 36.
AZT is not a new drug. It was not created for the treatment of
AIDS and is not an antiviral. AZT is a chemical compound that was
developed -- and abandoned -- over 30 years ago as a potential chemotherapy
treatment for cancer. (108) Prior to the first AIDS drug trials
in 1986, AZT had never been administered to human beings.
works by killing all growing cells in the body. Many cancer patients
do not survive chemotherapy due to its destructive effects on the
immune system and intestines. Because of the damage it causes, chemotherapy
is never used as a prevention for cancer, and is only administered
for very limited amounts of time.
This label has appeared on bottles containing
as little as 25 milligrams, a small fraction (1/20 to 1/60) of a
patient's daily prescribed dose of 500 to 1,500 mg. (109)
Since cancer is a condition of persistently growing cells, AZT
was designed to prevent the formation of new cells by blocking development
of DNA chains. In 1964, experiments with AZT on mice with cancer
showed that AZT was so effective in destroying healthy growing cells
that the mice died of extreme toxicity. (110) As a result, AZT was
shelved and no patent was ever filed. Twenty years later, the pharmaceutical
company Burroughs Wellcome (now Glaxo-Wellcome) began a campaign
to remarket AZT as an anti-HIV drug based on the idea that AZT would
block the formation of HIV DNA chains. Glaxo-Wellcome won FDA approval
for AZT as an AIDS treatment after one highly flawed study of only
four months duration. (111)
Approval of this extremely toxic chemotherapy for use by AIDS patients
was based on information that suggested AZT raised levels of T cells
and therefore delayed the onset of AIDS indicator diseases. The
rise noted in T cells was interpreted as evidence that AZT eradicated
HIV in T cells, a concept for which there is no scientific proof.
Although the study was halted before any long-term effects of AZT
were known, proponents established that standard treatment with
AZT should be continuous and lifelong.
A multitude of independent studies conducted before and after FDA
approval, including the Concorde study -- the largest (1,749 subjects)
and longest (three years in duration) study on AZT -- determined
that AZT increases T cell counts only moderately and briefly without
improving health and that it does not delay onset of AIDS indicator
The brief rise in T cells noted when AZT use is initiated is due
to the toxic nature of the drug and to the blood system's response
to the destruction of bone marrow. (113) As AZT destroys bone marrow,
the blood system attempts to correct this depletion by overproducing
T cells, often creating more new T cells than the number found in
a patient's blood prior to beginning treatment. But as the source
of these new T cells -- the bone marrow -- is killed off by AZT,
the level of T cells drops lower, ultimately causing complete destruction
of the immune system. Individual tolerance to, and absorption of
AZT determine length of survival on this toxic compound.
Following recommendations for "early intervention," one-third
to one-half of HIV positives who develop AIDS do so only after taking
AZT. Independent studies have shown that AZT actually accelerates
clinical decline and decreases quality of life, at times even causing
death before any AIDS-defining illnesses appear -- an occurrence
officially described as "death without any preceding AIDS-defining
concept of "HIV mutation" has become a popular explanation
for the fall in T cells observed in patients treated with AZT. Promoters
of the mutation hypothesis assert that the positive effects of AZT
are diminished by mutant strains of HIV that become resistant to
the drug. There is, however, no scientific evidence to substantiate
In addition to destroying T cells,
and the red blood cells that carry oxygen throughout the body, AZT
and other nucleoside analog drugs destroy the kidneys, liver, intestines,
muscle tissue, and the central nervous system. Nucleoside analog
drugs also interfere with the activities of mitochondria, the subcellular
particles that are the energy factories of every living cell in
the body. Mitochondria contain their own DNA which makes them vulnerable
to the effects of nucleoside analogs.
Epivir (3TC), Zerit (D4T), Hivid (ddC) and Videx (ddI) are all
nucleoside analog drugs prescribed to HIV positives as "antivirals."
All are modeled after AZT, and all work in the same manner.
Loss or reduction of the number of granulocytes, a group of white
blood cells that fight infection. These white blood cells contain
a variety of enzymes used to destroy infectious agents.
Generalized loss or reduction of white blood cells.
B cells: One of
two principle types of lymphocytes (white blood cells). B cells
are transformed into plasma cells that secrete immunoglobulins or
antibodies that destroy invading microorganisms. The protective
effect of immunoglobulins is called humoral immunity.
A synthetic compound similar to one of the components of DNA or
RNA. Nucleoside analogs such as AZT act as artificial caps to DNA
chains which prevent real DNA units from being added. For this reason
these drugs are often referred to as DNA chain terminators.
Protease inhibitors are a new class of AIDS drugs used in conjunction
with older chemotherapy compounds such as AZT and ddI. The mixture
of these treatments is called a "combination cocktail"
or "highly active antiretroviral therapy" (HAART). The
formula is usually two parts nucleoside analog to one part protease
inhibitor. According to popular belief, this mix brings new power
to the old chemotherapies, and achieves what press reports and AIDS
groups characterize as unprecedented and amazing results.
Approved after the fastest and most lenient review process in FDA
history and immediately hailed as miraculous by mainstream media,
the clinical benefits of protease inhibitor drugs remain unproved.
More than four years after being released for use, there are still
no reports in scientific journals that provide evidence of health
improvement in patients taking these powerful drugs.
Claims of victory for protease inhibitors are based entirely on
changes in surrogate markers, laboratory measurements of unsubstantiated
accuracy and value in assessing actual health. In the only published
report alleging higher survival rates for patients treated with
protease inhibitors, the study used no unmedicated placebo controls,
did not allow reporting of any recurrent AIDS-defining events except
pneumonia, included no patient data, cited outcomes for less than
10% of overall participants, and was prematurely terminated after
an average follow-up of 38 weeks when emerging mortality statistics
favored the protease inhibitor treated patients.115 The survival
outcomes between the two groups1.4% mortality among those on the
new drugs, 3.1% for the old drugs have no statistical significance,
a fact that forces the drug advertisements to admit "because
the study was ended early, there was insufficient data to determine
the statistical impact of Crixivan on survival."117
One National Institutes of Health study of protease inhibitors,
ACTG315, is portrayed as a success even though its conclusions are
drawn from a trial of only 12 weeks.118 Dr. Michael Lederman, protocol
chairman and author of ACTG 315 acknowledged that the study was
never designed to consider a patient's health. Instead, results
were determined by changes in the surrogate marker of "viral
load," a test that does not diagnose illness, quantify active
virus or measure health.
The absence of data on long-term effects of protease inhibitors
has not prevented orthodox AIDS organizations who promote or provide
the drugs from becoming uncritical advocates. Following the lead
of the media, their focus has been on securing widespread access
to the treatments rather than on examining evidence to insure they
are safe and effective. AIDS doctors have also overlooked the remarkable
lack of documentation in favor of the options for treatment offered
by protease inhibitors. And while boldface headlines continue to
assign lifesaving properties to these drugs, the tiny type in pharmaceutical
ads, the ever-growing list of side effects, and the increasing number
of unsuccessful experiences ranging from physical deformities to
sudden death tell an entirely different story.
Protease inhibitors are assumed to work by disrupting an enzymatic
link in the reproduction of HIV. Enzymes are proteins that join
together or cut apart other molecules. Like all retroviruses, HIV
has three enzymes: reverse transcriptase, integrase, and protease
which cut proteins apart, an essential step in the reproductive
process of a retrovirus. Protease inhibitors block proteases by
acting as dysfunctional molecules that take the place of functional
ones and inhibit the cutting apart of proteins. All retroviral enzymes
are similar to various human enzymes and there are numerous human
proteases, including ones required for digestion of food.
Protease inhibitors are like nucleoside analog drugs such as AZT
in that they produce dysfunctional substitutes that interrupt or
prevent normal processes of enzymes. While manufacturers of protease
inhibitors claim that the drugs specifically target HIV protease,
the growing list of side effects contradicts their assertions. Nucleoside
analogs such as AZT, once promoted as specifically targeting HIV,
have been shown to block the construction of vital human DNA as
effectively as they block the formation of HIV DNA. It is now known
that AZT, ddI and other nucleoside analogs block the DNA inside
mitochondria, the subcellar particles that produce the energy required
for the life of all cells.
The necessity for lifelong therapy with protease inhibitor cocktails
is described as absolute, although drug manufacturers clearly state
that "the long-term effects of protease inhibitors are unknown."
The need for rigorous compliance with combo therapy is a popular
subject of news reports and AIDS organization seminars. Patients
are required to pop as many as 30 pills a day on a 24 hour schedule
some taken with food, others on an empty stomach, many that cannot
be taken together and warned that without strict adherence to the
dosages and times, their virus will mutate into new, drug resistant
According to Dr. David Rasnick, a protease expert working outside
the AIDS system, the theory of resistant HIV protease is completely
unfounded. Rasnick, a pioneer in the development of protease inhibitors
points out, "no one has ever published data on a resistant
HIV protease found in any patient. The only inhibitor-resistant
HIV proteases ever examined have been produced in the lab using
Nevertheless, warnings about drug-resistant HIV proteases are emphasized
in media reports that also speculate about new epidemics that will
arise when unstoppable forms of HIV are introduced into the population.
As announced by AIDS researcher Dr. Bruce Walker on a recent segment
of ABC News' Nightline, "That's going to be the next epidemic
that we're dealing with, the transmission of drug resistant HIV
viruses."120 Such reports reinforce the notion that no matter
how unbearable the side effects, a patient who quits the drugs becomes
a public health menace. This science-fiction scenario has even inspired
some health officials and legislators to consider mandatory treatment
laws for HIV positives.121
Perhaps the greatest achievement of protease inhibitors is the
new life they have given to AIDS advertising campaigns. An epidemic
of posters, billboards, and full-page magazine ads urge HIV positives
to "be smart about HIV" by "hitting early and hard"
with medicines "proven to help people live longer, healthier
lives."122 However, many staunch supporters of AIDS pharmaceuticals
are less certain. Top AIDS scientist Dr. Anthony Fauci expressed
serious reservations about the use of protease inhibitors by "otherwise
healthy people" in a recent article in the Journal of the American
Medical Association, "We do not know whether early intervention
in asymptomatic individuals will result in a long-term clinical
benefit or whether the cumulative toxicity over years of drug administration
will outweigh the potential benefits."123 Even Dr. Robert Gallo
has warned that "these drugs are toxic...the longer you take
the drugs, the greater the toxicity."124 Dr. Jay Levy, another
mainstream AIDS specialist, maintains that "these drugs can
be toxic and can be directly detrimental to a natural immune response
A careful examination of the small print in protease inhibitor
ads puts the promises made by smiling models into perspective: "Since
Crixivan has been marketed, other side effects have been reported
including rapid breakdown of red blood cells, kidney stones and
kidney failure. In some patients with hemophilia, increased bleeding
has been associated with protease inhibitor use."126 Pre-marketing
side effects like diarrhea, nausea, fungal infections, bloody urine,
weakness, headaches and liver inflammation were all but ignored
by AIDS activists who pressured the FDA for fast-track approval.127
The list of post-marketing side effects continues to grow and contradicts
earlier reports on the cocktails that proclaimed, "It's unbelievable.
There's no toxicity. It's a home run!"128
Documented adverse reactions presently include CMV retinitis (a
viral infection that often results in blindness), diabetes, liver
failure, physical deformities, renal failure, kidney sludge, skin
rashes, severe exhaustion, loss of appetite, ,
diarrhea, nausea and vomiting, muscle and joint pain, ,
sexual dysfunction, fever, chills, dizziness, abdominal pain, depression,
sleep disorders, and sudden death.129
Other than anecdotal tales of miraculous recoveries trumpeted in
the press, the lower levels of "viral load" found in some
patients taking protease cocktails seem to be the only and highly
questionable result of these treatments. But even "undetectable"
viral loads are not an unprecedented occurrence in HIV treatment.
AZT has lowered those levels for many years without resolving AIDS.
A POZ magazine article recalls that "in the European Delta
study, fully 40% of participants became 'undetectable' [for viral
load] on AZT/ddI; another 5% did so on AZT alone. We have been reducing
viral load to undetectable levels for a decade. But if becoming
'undetectable' on nucleoside combos hasn't prevented progression
to disease and death, why is 'undetectable' on protease combinations
impervious to failure except for the fact that we haven't followed
patients long enough to see it?"130
Although the media credits "AIDS cocktails" with recent
decreases in AIDS cases and deaths, CDC surveillance reports clearly
show that AIDS cases and mortalities have been steadily declining
since 1993 almost three years before the cocktails were approved
for use.131 Some experts like David Rasnick attribute the drop in
AIDS deaths that began in 1993 to the fact that over half of all
AIDS cases reported since that year are among people who test HIV
positive but have no illness or symptoms.132 The same reports show
that AIDS cases had leveled off in 1991 and increased only once
since, in the first quarter of 1993 when more conditions and illness
were added to the definition of AIDS.
For some, the chorus of enthusiastic press reports about protease
inhibitors recalls the release of AZT twelve years ago. "Once
again, all we have are researchers talking to reporters about incomplete
studies that haven't been scrutinized by the scientific review process,"
remarks Dr. Rasnick. "And the researchers involved are funded
by the companies that make the drugs in question. There is no justification
for the claims coming from these sources, particularly when we've
seen it all before."133
of success and improved survivability for AZT were based on abbreviated
trials of less than six months duration that were sponsored by the
drug's manufacturer who selected for publication only those trials
with seemingly favorable outcomes. Success was measured by the surrogate
marker of that day, increased T cell counts, which have proved to
be a temporary phenomenon at best and of questionable clinical value.
As with AZT, the elation unleashed over protease inhibitors is based
on unpublished manufacturers' studies so brief they are usually
measured in weeks rather than months, and on the surrogate marker
of reduced "viral load," a measurement that has not been
correlated with actual health benefits. While the media persists
with stories of the miraculous achievements of protease inhibitors
making believers out of the concerned public and desperate AIDS
patients, only time and independent research will reveal the truth
about the latest "great hope" in the war on AIDS.
Inflammation of the pancreas; chronic pancreatitis often causes
disease or disorder of the nervous system.
A laboratory test result that takes the place of or substitutes
for a clinical indication or diagnosis.
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