ZAMBIA: COVER STORY
A
rash of complaints ...the tragic side-effects of
Aids drugs
Tragic underestimation of flesh-sloughing side-effects
and failures in patient
monitoring led to the deaths which forced South
Africa to halt the clinical trials of
the anti-Aids drug, Nevirapine, in April this
year.
A ghastly side-effect called Stephens-Johnson
Syndrome (SJS) first start as a rash
but kills patients after eating up their flesh
in serious cases.
Official data available before the clinical trials
commenced showed that Nevirapine
was five times more likely to cause the deadly,
drug-induced SJS than was the more
expensive AZT, which equally has deadly toxic
side-effects.
SJS killed two of the five women in the South
African trials, appearing within weeks
of commencing Nevirapine — at first as a rash
(but all the skin can be sloughed off),
mouth and trachea blisters, and lungs and intestines
can shed layers inside the body.
Prevention of side-effects requires careful patient
monitoring. By far the most
common complication is described as “rash” when
mild, or as SJS when severe.
Immediate withdrawal of Nevirapine is mandated
in all but mild reactions.
On 6 April this year, the PAC chief whip in South
Africa, Patricia de Lille, said that
she had uncovered a “nest of abuse and exploitation”
in clinical trials of anti-Aids
drugs in the country.
Participants in the trials told De Lille of severe
side effects and irregularities in the
way patients were asked to sign consent forms
they did not understand.
In an interview with The Natal Witness, De Lille
said: “One patient developed a rash
all over the body and still has marks on the
face. He told [the doctor in charge of the
trials at the Kalafong Hospital in Pretoria]
that this had happened since using the
drugs, but the doctor said it was not the drugs
causing the rash, but the HIV virus”.
The Natal Witness also quoted De Lille saying
that one woman went completely
blind for two weeks, but regained her eyesight
after discontinuing the drugs.
Before De Lille’s remarks were even reported,
the South African health minister,
Manto Tshabalala-Msimang (who is a medical doctor
herself) announced a halt to
the Nevirapine trials. She told parliament that
two of the five women died of liver
damage, and there was a “probable” causal association
with Nevirapine in the other
three cases.
But Kevin McKenna, a spokesman for the Nevirapine
manufacturers, Boehringer
Ingelheim, was not about to own up. “My information
is that the actual link to
Nevirapine is inconclusive, and that the company
involved is examining the [deaths]
and establishing the reasons”, he said at the
time.
But Boehringer itself had said on a New Zealand government website that:
“The major clinical toxicity of Viramune [another
name for Nevirapine] is rash,
occurring in 16% of patients; [in one study
as much as] 35% of patients experienced
rash...
“Severe or life-threatening rash occurred in
6.6% of Viramune-treated patients...
Severe or life-threatening skin reactions have
occurred in patients treated with
Virumune, including SJS and TEN (toxic epidermal
necrolysis). Fatal cases of SJS,
TEN and hypersensitivity reactions have [also]
been reported.
“Severe and life-threatening hepatotoxicity,
including fatal fulminant hepatitis, has
occurred in patients treated with Viramune.
Some of these cases began in the first
few weeks of therapy. Monitoring of liver function
tests is strongly recommended
especially during the first six months of Viramune
treatment.”
But what Boehringer does not say is that the
“hepatotoxicity” arises partly because
the liver is the organ that must metabolise
Nevirapine. Deaths from liver failure are
not unheard of in such clinical trials, but
are certainly minimised by proper
monitoring.
So, two of the five deaths that occurred in the
Nevirapine trials in South Africa can
be accounted for by “hepatotoxicity” as the
health minister indicated in parliament.
But what about the three other deaths described
as “inconclusive” by the Boehringer
spokesman?
More than a rash
Describing the side-effects of Nevirapine as
a “rash” is misleading. Because the
“rash” is neither cutaneous nor arising from
localised causes, but systematically
driven; and means the body is signalling a very
serious illness. In the severe forms of
Nevirapine effect, the reaction progresses in
ways that depart from any known
“rash”.
A Carte Blanche TV documentary shown in South
Africa recently said one patient,
Rebecca, “went completely blind for two weeks.”
Q: “What happened to your sight after you took the pills?”
Rebecca: “I started to change. Blind... not hear[ing]
nicely... not speak[ing]
properly.”
Rebecca also said she witnessed other symptoms,
including anal bleeding, sores that
would not heal, abdominal pains, weight loss,
fevers and pneumonia. These could all
be typical Aids symptoms, but Rebecca remains
convinced it was the drug, not the
virus.
But these were no Aids symptoms. The rashes and
sores observed were classic
Nevirapne rash. The anal bleeding and abdominal
pains bore testimony to
Nevirapine’s predilection for affecting the
gastrointestinal system as seen in the
comparable clinical trial which ushered in the
US Food and Drug Administration
(FDA) approval of the drug on 24 June 1996.
The full blindness was untreated SJS ocular sloughing.
The blindness which,
tellingly, healed on stopping medication was
a reversal of SJS.
These concerns are taken seriously in the European
Union. On 12 April this year,
the European Agency for the Evaluation of Medecines
decided to maintain
Nevirapine in its “under exceptional circumstances”
category.
Based on “continuing reports on incidents of
these very severe reactions in
1999/2000”, the European Agency issued an “urgent
safety restriction” on
Nevirapine to include new warnings on “life-threatening
cutaneous and hepatic
reactions”.
In America, patients are advised to “dial 911
or rush to the nearest ER” on suspicion
of an SJS reaction.
A prudent person would ask whether medication
requiring this level of support
services is in any way appropriate for Africa.
Against this backdrop, it is worrying that the
Carte Blanche investigation reported
problems with access to the medical files of
the patients involved:
Nelly: “They say the file is missing.”
Carte Blanche: “The hospital registry told Nelly
that her files were removed from
the registry.”
Case closed?
Fintan Dunne
Editor (Aidsmyth.com)
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