SEROPOSITIVITY AND MORTALITY IN PERSONS WITH HAEMOPHILIA;
PROOF THAT HIV CAUSES AIDS?
Papadopulos-Eleopulos,1 Valendar F.Turner,2
Bruce Hedland-Thomas,1 David Causer,1
and John M. Papadimitriou3
of Medical Physics, (2) Department of Emergency Medicine, Royal
Perth Hospital, Box X2213 Perth, Western Australia 6009; (3) Department
of Pathology, University of Western Australia.
In a study
published by a large group of epidemiologists, of British haemophiliacs
(Nature, September 7th), it is claimed that "During
1985-92, there were 403 deaths in HIV seropositive patients, whereas
60 would have been predicted from rates in seronegatives suggesting
that 85% of the deaths in seropositive patients were due to HIV
infection". In the accompanying Nature editorial it
is said that this "thorough study", "will, for most
people, be sufficient proof that the infection [HIV] leads to AIDS".
However most people are not scientists and for scientists "suggesting"
is not proving.
One can claim
that the 85% increase in death rate amongst seropositive haemophiliacs
is due to HIV if, and only if, the study had evidence which showed
(1) The cause
of death in the 343 extra deaths in the seropositive patients was
AIDS, otherwise one will have to show that in haemophiliacs HIV
does not cause only AIDS but all the other diseases from which these
(2) All the
patients who died from "AIDS" were infected with HIV.
(3) HIV causes
leading to mortality
A glance at
table 3 where "cause-specific mortality during 1985-92"
is given, it shows that of the 403 deaths in seropositive individuals,
168 died from causes other than AIDS. The other 235 died from "AIDS,
HIV, etc". The statement that deaths were due to "HIV,
etc" is meaningless.AIDS stands for Acquired Immune Deficiency
(AID) on the one hand and the syndrome (S) on the other. Because
the syndrome is constituted from more than 25 diseases and because
no other single, infectious agent is posited as the cause such a
panoply of distinct and unrelated diseases including infections
and neoplasms, it is said that the syndrome is caused indirectly.
That is, HIV causes Acquired Immune Deficiency which in its turn
leads to the appearance of the Syndrome. It is accepted that in
AIDS, AID stands for decreased T4 (helper) cells resulting from
their destruction by HIV.
study there is no evidence that the 235 patients had a low T4 cell
count due to their destruction by HIV or any other agent. In fact,
at present there is no evidence that the T4 cells of haemophiliacs
or for that matter, any AIDS patients, are destroyed either by HIV
or any other agents, or that a causative relationship exists between
a decrease in T4 cells and the appearance of the clinical syndrome
(1). In fact no agreement, or even evidence, exists that lymphocytes
contain two subsets, T4 and T8 which have exclusive roles, T4 as
helpers and T8 as suppressors, a fact acknowledged by immunologists
from many institutions including the University of Stockholm and
the Institut Pasteur (2, 3). As far back as 1981 James Goodwin,
from the University of New Mexico, wrote: "The T- and B-cell
measurers - having run through the sick, the elderly, the young,
the pregnant, the bereaved - had finally run out of diseases......
And now it's starting all over again, this time with T-cell subsets......
Why not let us unimaginative immunologists publish to our heart's
content?...... My strongest argument is this: Measurement of T and
B cells and their subsets in disease has no clinical meaning.........
But most non/immunologists do not realise this........ Nonimmunologists
have naturally assumed that any subject occupying so much Journal
space must be relevant in some way - a logical but incorrect assumption"
of the diseases which constitute this syndrome is new or specific
to it. The diseases which are rare in the general population and
most often diagnosed in AIDS are two: Kaposi's sarcoma (KS) and
Pneumocystis carinii pneumonia (PCP). In fact these two diseases
constitute the basis for the HIV hypothesis of AIDS. However, although
in the Nature studies it is not stated how many, if any, British
haemophiliacs have died from KS, it is a known fact that unlike
gay men, haemophiliacs rarely, if ever, died from KS. The clinical
picture of PCP is not specific to this disease, both infectious
and non-infectious diseases produce clinical pictures comparable
with PCP. Neither can the disease be diagnosed by radiological means.
Before the AIDS era, and even in the early 1980's, the visualisation
of the causative organism P. carinii in Gomori-methenamine salver
(GMS) stained preparation of lung tissue obtained by open lung biopsy
was considered the only method suitable for a definite diagnosis
of PCP. Even with this method "considerable expertise is necessary
to differentiate P. carinii from other GMS positive entities, particularly
yeast".(5) In the AIDS era, the method used to diagnose PCP
became less and less specific. Instead of open lung biopsy, diagnosis
began to be obtained by fibreoptic bronchoscopy, a much "less
dependable" procedure, or bronchoalveolar lavage (BAL). However,
"one might expect to find P. carinii in the fluid from bronchoalveolar
lavage of about 40% of patients with AIDS who present with symptomatic
pneumonia caused by other organisms".(6) Despite the very high
level of false positive results obtained with BAL, this procedure
is not only used to definitely diagnose PCP but, more recently,
as a gold standard for other, even less specific procedures used
for the "definite" diagnosis of PCP, such as testing specimens
from sputum induction using GMS.(7) In turn this procedure is used
as a gold standard for the "definite" diagnosis of PCP
by testing sputum specimens with the use of "monoclonal antibodies".
Instead of GMS, although it is accepted that in sputum specimens
GMS "will stain not only P. carinii but also host and microbial
cells and amorphous debris, which make up a large part of the sputum
sample; even in experienced hands, distinguishing P. carinii from
this background can be difficult".(8) Another method presently
used for the "definite" diagnosis of PCP is the polymerase
chain reaction. However, the authors themselves admit that this
method, when compared to detection of P. carinii in BAL or sputum
specimens, as gold standard, this procedure is less specific and
"most falsely positive samples were from patients treated with
immunosuppressive drugs or from HIV- positive patients with CD4
counts below 0.2 x 109/".(9) Nonetheless, on the basis of these
tests, individuals from the AIDS risk groups, including haemophiliacs
are diagnosed as having PCP and are treated accordingly. Some studies
recommend the use of "empiric therapy for PCP, based purely
on" clinical findings. But, "The propensity of patients
with PCP to present with atypical clinical finding, the ability
of both infectious and non-infectious diseases to produce a clinical
picture compatible with PCP, and the toxicity of anti-pneumocystis
treatment regimes however, all argue against the use of empiric
treatment based on clinical evaluation alone".(5) The toxic
effects include "neutropenia, thrombocytopenia, or both",
(6) which are of particular significance to haemophiliacs since
these diseases were present in high frequency in this population
long before the AIDS era, and thrombocytopenia is considered to
be a contributing factor in the development of AIDS in haemophiliacs.(10)
In conclusion from the study it is not possible to say how many
of the 235 haemophiliacs died from KS and PCP, considered to be
the most specific AIDS diseases; from "mild and moderate diseases",
which following the 1985 CDC AIDS definition signified AIDS; from
AIDS defining conditions according to the 1987 CDC definition (according
to which a patient could have been certified as dying from AIDS
without a definite disease diagnosis or even with no evidence for
HIV infection and even against HIV infection); or from "AIDS"
in general whatever one means by it.
CAUSE Of the
343 extra deaths in HIV seropositive haemophiliacs between 1985-92
only 235 were due to "AIDS, HIV, etc". To account for
the other 168 extra deaths one will have to assume that either:
(1) In haemophiliacs
HIV does not cause only AIDS but all the other diseases for which
the 168 patients died.
(2) In the
AIDS era two, or more, new pathogens appeared in haemophiliacs,
HIV which caused the 235 deaths and the other(s) which caused the
other 168 diseases.
(3) The extra
deaths in haemophiliacs, including the 235 who died from "AIDS,
HIV, etc" were caused by agents other than HIV.
The only evidence
which one can find in the study for a causal role of HIV in haemophilia
deaths is that most of the deaths occurred in seropositive haemophiliacs.
However, as it has correctly been pointed out in the editorial,
"It is well known that no amount of statistical argument can
by itself prove that a disease is actually caused by the agent with
which it is statistically associated:. Indeed before one can claim
that "85% of deaths in seropositive patients were due to HIV
infection", one must satisfy two conditions:
evidence that the "seropositive patients" were actually
infected with HIV, that is, the antibody tests are HIV specific.
by direct evidence, not by association, that the "85% of deaths"
were caused by HIV. There are two major problems in using "seropositivity"
to diagnose HIV infection:
The only way
to determine the specificity of the antibody test for HIV infection
is to use viral isolation as a gold standard. This has never been
reported and in fact there is ample evidence that the tests are
non-specific (11). That this is the case in haemophiliacs is acknowledged
by very well known HIV/AIDS researchers (12-14). Even the CDC accepts
that a positive test in haemophiliacs is not proof of HIV infection.
"It is possible that antibody to LAV is acquired passively
from immunoglobulins found in factor VIII concentrates..... Likewise,
it is possible that seropositivity is caused not by infectious virus
but by immunisation with noninfectious LAV or LAV proteins derived
from virus disrupted during the processing of plasma into factor
VIII concentrate" (15).
the authors of the epidemiological study, "A reliable test
for HIV antibodies became available to Haemophilia Centres early
in 1985. Among those who were alive on 1st January 1985,
78% of potentially infected severe patients and 52% of moderate/mild
patients had been tested by December 1985, rising to 90 and 74%
respectively by January 1993. One thousand and twenty severe patients
and 207 moderate/mild patients were found to be infected..... The
median estimated date of seroconversion was October 1982 for severe
patients......and December 1982 for moderate/mild patients".
Before 1987 a positive ELISA with or without a WB was considered
proof of HIV infection. However, it was realised that many individuals
(4000/6000 [67%] in one study (16), who had a positive ELISA did
not test positive when the WB was performed. This was interpreted
as evidence that the WB was more specific than the ELISA, and since
1987 many, but not all, laboratories use ELISA only as a screening
test and WB as confirmation. But in addition to the fact that the
specificity of the WB has never been determined, there are many
other problems associated with the use of this test to prove HIV
infection, so much so, that according to Philip Mortimer, "Western
blot detection of HIV antibodies began as and should have remained,
a research tool"(17). Among the many problems associated with
the WB is the arbitrary introduction of criteria as to which WB
pattern means HIV infection. At present these criteria vary between
continents, between countries and even between laboratories in the
same country. The criteria have also changed over time. It is of
pivotal significance that the criteria used to define a positive
WB before 1987, by which time most of the haemophiliacs were tested
and were found to be positive, would not satisfy even the "least
stringent" criteria presently used to define a positive WB
(1) The study
presented no evidence that the 235 seropositive haemophiliacs died
from AIDS, whichever definition is chosen, merely the bold assumption
that they died from "AIDS, HIV, etc".
(2) The study
presented no evidence that the excess in the seropositive patients
were caused by HIV, or even that the haemophiliacs were infected
(3) The most
one can claim from the evidence presented is that the finding of
positive "HIV antibody" test, whatever that signifies
(but certainly not HIV infection of haemophiliacs via factor VIII),
indicates an underlying abnormal propensity to develop a number
of illnesses which may prove fatal.
(4) The study,
more than anything, highlights the urgent need to:
the meaning of a positive "HIV antibody" test in haemophiliacs;
effects which factors associated with "HIV antibodies"
may have on the health of persons with haemophilia. These include
lifetime exposure to factor VIII and impurities in clotting concentrates,
prophylactic and therapeutic anti-bacterial and anti-viral agents,
AZT, blood transfusions, steroids and also the psychological impact
of a diagnosis of HIV seropositivity (18, 19).
In any scientific
debate both sides have obligations, the antagonist to question when
there is indisputable evidence that contradicts the received wisdom;
the protagonist to answer these questions rather than simply to
One such question
rises from the following laboratory data:
1. There is
unanimity that gp120, a component of the knobs on the surface of
HIV is an absolute prerequisite for "HIV infection" (20,
2. Such knobs
are found only in immature (budding) particles which are "very
rarely observed", and are absent in cell-free HIV (22, 23)
thus rendering cell-free HIV non-infectious.
to Professor R. Penny, Australia's leading HIV/AIDS expert, "HIV
is rapidly inactivated in discarded needles and syringes" (24);
4. Levy and
his colleagues have shown that the titre of HIV in plasma of HIV
infected individuals three, six or twelve hours after phlebotomy
"dropped from up to 500 TCID/ml to 0" [TCID=tissue culture
infectious dose] ;
5. In January
1994, the CDC (25) communicated the following experimental data
and conclusion: "In order to obtain data on the survival of
HIV, laboratory studies have required the use of artificially high
concentrations of laboratory grown virus...the amount of virus studied
is not found in human specimens or anyplace else in nature,...it
does not spread or maintain infectiousness outside its host. Although
these unnatural concentrations of HIV can be kept alive under precisely
controlled and limited laboratory conditions, CDC studies have shown
that drying of even these high concentrations of HIV reduces the
number of infectious viruses by 90 to 99 percent within several
Since the HIV
concentrations used in laboratory studies are much higher than those
actually found in blood or other body specimens, drying of HIV-infected
human blood or other body fluids reduces the theoretical risk of
environmental transmission to that which has been observed-essentially
in most instances, if not all, the time between phlebotomy and conversion
of pooled plasma to factor VIII concentrate is considerably greater
than 3 hours; (b) factor VIII is made from plasma which is cell
free; (c ) the late 1970s factor VIII has been supplied as a dry
powder which may spend weeks or months waiting use; how can one
reconcile the above facts with the view that haemophiliacs are infected
with HIV via contaminated factor VIII concentrates?
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