T4 and the clinical syndrome

The HIV/AIDS researchers consider T4 decrease as being the "hallmark" and
"gold standard" of HIV infection and AIDS (Shaw et al., 1988; Levacher et
al., 1992). In fact, in the most recent (1992) CDC AIDS definition, an
AIDS case can be defined solely on serological, (positive HIV antibody
test), and immunological (T4 cell count less than 200 X 106/L), evidence
(CDC, 1992). The new definition also requires that "the lowest accurate,
but not necessarily the most recent, CD4+ T- lymphocyte count should be
used" to define an AIDS case (CDC, 1992). However, ample evidence exists
that T4 cell decrease can be induced by many factors, some trivial, such
as sun bathing and solarium exposure, a decrease which can persist for at
least two weeks after exposure has ceased (Hersey et al., 1983; Walker &
Lilleyman, 1983). T4 cell counts "can vary widely between labs or because
of a person's age, the time of day a measurement is taken, and even
whether the person smokes" (Cohen, 1992). That many factors can affect the
T4 cell number is reflected by their large variation in HIV positive
patients. In one such study, patient measurements repeated by one
laboratory within 3-days showed a "minimum CD4+ cell count of 118
cells/mm3 and a maximum CD4+ cell count of 713 cells/mm3" (Malone et al.,
1990). In the MACS, consisting of 4954 "homosexual/bisexual men", it was
stressed that physicians and patients should be "aware that a measured CD4
cell count of 300X106/L really may mean it is likely that the "true" CD4
cell state is between 178 and 505X106/L. Thus there is no certainty this
person's "true CD4" is less than 500X106/L or that it is greater than
200X106/L" (Hoover et al., 1992). It is important to note that these
variations were obtained despite the fact that the CD4 measurements were
undertaken in laboratories which "are carefully standardized in an ongoing
quality control program".

In a study (Brettle et al., 1993) which examined the impact of the 1993
CDC AIDS definition on the annual number of AIDS cases as compared to the
1987 definition, it was found that if the definition was based on:

(i) the "first of two consecutive CD4 cell counts < or equal to 200 X
106/L", the number of AIDS cases doubled;

(ii) one abnormal CD4 count, the number of AIDS cases trebled.

Researchers at the University of California at Los Angeles School of
Medicine found that 5% of healthy persons seeking life insurance had
abnormal T4 cells counts, and that "In a subgroup of patients, the low
T-cell numbers or ratios appear to be stable findings". They concluded:
"In the absence of a history of a specific infection or illness or major
abnormalities on a physical examination, it is not worthwhile to attempt
to find a specific cause for the abnormality of T- cell subsets...A
uniform approach to this problem throughout the medical community will
help alleviate patients' anxiety and reduce the concern of the insurance
industry about this relatively common problem" (Rett et al., 1988).

If LAS, ARC, and the AIDS indicator diseases such as KS and PCP are the
consequence of T4 cell depletion then all groups of people who have a low
T4 cell count, irrespective of cause, should have high frequencies of
opportunistic infections and neoplasms. Conversely, all patients with AIDS
indicator diseases should have abnormally low T4 cells.

In a study on the effects of blood transfusion on patients with
thalassaemia major, researchers at the Cornell University Medical Center
and the Sloan-Kettering Institute for Cancer Research observed decreased
T4 cell numbers and inverted T4/T8 ratios associated with the
transfusions, but no increase in KS or PCP, and concluded that "...studies
which define transfusion related AIDS on the basis of analyses with
monoclonal antibodies must be viewed with caution" (Grady et al., 1985).
Although patients with alcoholic liver disease do not develop KS, PCP and
other AIDS indicator diseases more often than usual, they have both immune
deficiency and positive HIV antibody tests leading researchers from the
Veterans Administration Medical Centre to stress the importance of
recognising these facts: "...lest these patients be falsely labelled as
having infection with the AIDS virus and suffer the socioeconomic
consequences of this diagnosis" (Mendenhall et al., 1986).

Patients who have malaria have severe immunoregulatory disturbances
including decrease in T4 cells. A significant number of these patients
also test positive for HIV but they do not develop the AID clinical
syndrome, leading Volsky et al to conclude, "exposure to HTLV-III/LAV or
the related retrovirus and the occurrence of severe immunoregulatory
disturbances may not be sufficient for the induction of AIDS" (Volsky et
al., 1986).

The MACS in the USA showed that "even in the absence of treatment, close
to 25, 15 and 10% of men were alive and asymptomatic 4, 5 and 6 years
after first CD4+ <200 X 106/L measurement" (Hoover, 1993). In the same
study comparing HIV positive individuals who within five years progressed
to AIDS (Group A) with that those who did not (Group B), it was found
that: "receptive anal intercourse both before and after seroconversion
with different partners was reported more frequently by men with AIDS. The
ratio of the differences in this sexual activity between groups A and B
was higher at 12 (2.3) and 24 (2.6) months after seroconversion than
before seroconversion (2.0)". It was concluded that "sexually transmitted
co-factors, preseroconversion and/or postseroconversion...augment (or
determine) the rate of progression to AIDS" (Phair et al., 1992). However,
since:

(a) sexually transmitted infectious agents are bi- directionally
transmitted, that is, from the active to the passive partner and
vice-versa;

(b) in the above study the only sexual act directly related to the
progression to AIDS was passive anal intercourse (unidirectionally);

one would have to conclude that the "co-factors that augment (or
determine)" progression to AIDS are non-infectious. These findings are in
agreement with the oxidative theory of AIDS which claims that both HIV
phenomena (RT, virus-like particles, antigen/antibody reactions,
"HIV-PCR") and AIDS are caused by the many oxidative agents (including
semen), to which the AIDS risk groups are exposed (Papadopulos-Eleopulos,
1988; Papadopulos-Eleopulos et al., 1989a; Papadopulos-Eleopulos et al.,
1992a; Papadopulos-Eleopulos et al., 1992b) [PCR=polymerase chain
reaction].

According to Canadian researchers, "In TB as well as in lepromatous
leprosy, an immunosuppressive state will frequently develop in the host.
This state is characterised by T lymphopenia with a decreased number of T
helper cells and an inverted T-helper/T-suppressor cell ratio
...immunosuppression induced by the infection with M.tuberculosis can
persist for life, even when TB is not progressive" (Lamoureux et al.,
1987). Yet these patients do not have high frequencies of KS, PCP or other
AIDS indicator diseases. In other words, decrease in T4 cells is not
sufficient for the AIDS indicator diseases to appear. This is also
supported by evidence from animal studies. Experimental depletion of T4
cells in mice used as models for systemic lupus erythematosus in humans
did not lead to increased frequencies of neoplasms, nor did mice "develop
infectious complications, even though they were housed without special
precautions". In fact mice with low T4 cell numbers had "prolonged life"
(Wofsy & Seaman, 1985) It is also of interest that despite the
indispensable role attributed to T4 and T8 lymphocytes in antibody
production (helper and suppressor respectively), AIDS patients in the
presence of low numbers of T4 cells and high numbers of T8 cells, have
increased levels of serum gammaglobulins, and are not
hypogammaglobulinaemic as might be expected. Also, although human
umbilical cord T-cells produce suppressor factors(s), the factor(s) is
produced by T8- (T4+) not T8+ cells (Cheng & Delespesse, 1986). Thus, T4
and T8 cells do not seem to possess the generally accepted functions
attributed to them.

According to the HIV theory of AIDS pathogenesis, "The Human
Immunodeficiency Virus (HIV), the etiologic agent of the acquired
immunodeficiency syndrome (AIDS), has the capability of selectively
infecting and ultimately incapacitating the immune system whose function
is to protect the body against such invaders. HIV-induced
immunosuppression results in a host defense defect that renders the body
highly susceptible to "opportunistic" infections and neoplasms" (Fauci,
1988). Decrease of T4 cells to approximately 200X106/L leads to the
development of "constitutional symptoms", and to less than 100X106/L to
"Opportunistic diseases" (Pantaleo et al., 1993). If this is the case
then:

1. In all individuals with "constitutional symptoms", OI and neoplasms,
the T4 cell number should be abnormally low;

2. The decrease in T4 cells should precede the development of the clinical
symptoms since: (a) the cause must precede the effect; (b) for many
neoplastic and infectious diseases, there is evidence that the diseases
themselves and the agents used to treat them may induce immune suppression
including decreased numbers of T4 lymphocytes and reversal of T4/T8
ratios.

This is not the case even for the most serious and characteristic of the
AIDS diseases, KS and PCP. In the MACS it was reported that:

(a) "...persistent generalised lymphadenopathy was common but unrelated to
immunodeficiency", and "Although seropositive men had a significantly
higher mean number of involved node groups than the seronegative men (5.7
compared with 4.5 nodes, p<0.005), the numerical difference in the means
is not striking".

(b) weight loss, diarrhoea, fatigue, fever, which constitute the "wasting"
syndrome, (which at present is an AIDS indicator disease), night sweats,
herpes zoster, herpes simplex (another AIDS indicator disease), oral
thrush, fungal skin infections and haematological abnormalities, were
present in both seronegative and seropositive individuals, although some
of them were present at higher frequencies in the latter group. A
relationship was found between thrush, anaemia, fever and neutropenia and
T4 cell deficiency. However, "the clinical abnormalities were considerably
better at reflecting concurrent CD4 lymphocyte depression than the low CD4
lymphocyte counts were at determining clinical involvement" (Kaslow et
al., 1987). These observations are just as compatible with the hypothesis
that T4 lymphocyte deficiency is the result and not the cause of the
observed clinical abnormalities.

KS, the main reason for which the retroviral hypothesis was put forward,
was initially postulated to be caused by infection of normal cells with
the retrovirus. When, late in 1984 it became clear that the KS cells were
not infected with HIV, it was generally accepted that the disease was
caused by HIV indirectly, that is, as a consequence of T4 cell decrease.

At present, it is generally believed that KS is caused by "a specific
sexually transmitted etiologic agent" (Beral et al., 1990; Weiss, 1993)
other than HIV, but "immune suppression (both in AIDS and in transplant
patients) is the dominant cofactor for subsequent disease" (Weiss, 1993).
However, unlike the Unites States CDC and most AIDS centres around the
world, for the Walter Reed Army Institute of Research "...the presence of
opportunistic infections is a criterion for the diagnosis of AIDS, but the
presence of Kaposi's sarcoma is omitted because the cancer is not caused
by immune suppression..." (Redfield & Burke, 1988) In a study by a group
of researchers from Amsterdam regarding the relationshipbetween the T4
cell number and the development of the clinical syndrome, KS was excluded
"Because Kaposi's sarcoma may manifest at higher CD4+ lymphocyte counts
than other AIDS- defining conditions" (Schellekens et al., 1992). This is
not surprising since by the beginning of the AIDS era, the immune
surveillance hypothesis of carcinogenesis had been already refuted
(Kinlen, 1982). In fact, the presently available data indicate that KS in
all individuals, including gay men, may be caused by a non-infectious
agent (Papadopulos-Eleopulos et al., 1992a). Even in the early stages of
the AIDS era, it was reported that KS in gay men appeared following
corticosteroid administration (which was administered for diseases totally
unrelated to HIV or AIDS) and resolved when the drug was discontinued
(Schulhafer et al., 1987; Gill et al., 1989). Thus the HIV/AIDS hypothesis
cannot account for the very disease for which it was originally put
forward.

In a study of 145 patients, 97% of whom were homosexuals, with biopsy
proven PCP at St. Vincent's Hospital and Medical Centre, New York, 17% of
AIDS patients had a T4 cell count higher than 500/mm3, and a further 14%
between 301-500/mm3, "in addition, patients with T4-T8 ratio greater than
1.0 and those with total T4 lymphocyte counts greater than 500/mm3 cells
did not show improved survival compared with patients with abnormal
values....the degree of suppression did not influence mortality (Kales et
al., 1987). Researchers from the National Institute of Allergy and
Infectious Diseases and the National Cancer Institute, studied 100
HIV-infected patients "who had 119 episodes of pulmonary dysfunction
within 60 days after CD4 lymphocyte determinations". T4 cells were less
than 200X106/L before 46 of 49 episodes of PCP, 8 of 8 episodes of CMV
pneumonia, 7 out of 7 Cryptococcal neoformans pneumonia, 19 of 21 episodes
of Mycobacterium avium-intracellulare pneumonia, 6 of 8 [pulmonary] KS and
in 30 out of 41 non-specific interstitial pneumonia. However, "Before the
119 episodes of pulmonary dysfunction were diagnosed in this study, the
HIV- infected patients had manifested the following clinical HIV- related
disorders: no disorders (4 episodes), Kaposi's sarcoma without
opportunistic infections (68 episodes), life- threatening opportunistic
infection (44 episodes), other AIDS- related conditions (11 episodes)". In
addition before the diagnosis of the pulmonary episodes the patients had
received: "zidovudine (36 episodes), interferon (23 episodes), recombinant
interleukin-2 (3 episodes), cytotoxic chemotherapy (16 episodes),
dideoxycytidine (6 episodes), muramyl tripeptide (1 episode), suramin (6
episodes), heteropolyanion 23 (5 episodes), zidovudine plus interferon (5
episodes), nonablative bone marrow transplantation (4 episodes). Twenty-
two episodes occurred in patients who had been receiving neither
experimental therapy nor zidovudine" (Masur et al., 1989). These data may
be interpreted as showing that in some types of "pulmonary dysfunction",
most cases (but not all) appear to be preceded by a CD4 count <200X106/L.
However, given the well known fact that malignant neoplasms, infectious
diseases and the administration of chemotherapeutic agents may themselves
cause immunosuppression (Serrou, 1974; Oxford, 1980; Reinherz et al.,
1980; Rubin et al., 1981; Thomas, 1981; Weigle et al., 1983; Williams et
al., 1983; Kempf & Mitchell, 1985; Feldman et al., 1989), it is equally
plausible to argue that both "pulmonary dysfunction" and the low CD4 cell
counts observed in patients were the result of their recent past illnesses
and previous exposure to prescribed and illicit drugs and other factors.

In a recent study it was found that 3 patients who developed PCP within
8-14 days of "symptomatic, primary HIV infection", had normal T4 cell
numbers and T4/T8 ratios 50-90 days before they became symptomatic. During
the symptomatic phase the T4 cell count dropped to 62-91 cells/uL.
However, "Within four months of symptom onset, their CD4 counts and
CD4/CD8 ratios returned to normal". In two of the patients, a bisexual man
and a gay man, "HIV-1 antibodies were detectable by EIA and WB" 30 days
after these two individuals became symptomatic [EIA=ELISA].

"Twenty-nine to forty-eight months after acquiring HIV-1 infection", all
three patients still had normal T4 cell numbers and were asymptomatic. The
authors concluded "profound CD4 lymphocytopenia can revert to normal
without antiretroviral therapy" and stressed "it is important that such
cases are not misdiagnosed as AIDS" (Vento et al., 1993).

That no relationship exists between OI and T4 depletion was confirmed in a
recent study where it was shown that "The appearance of OI and wasting
syndrome was independent of T4 cells count" (Alejandro et al., 1991), as
well as other studies which show that the OI may appear in the presence of
normal T4 cell numbers (Stagno et al., 1980; Martinez et al., 1991; Felix
et al., 1992).

In conclusion, decrease in the number of T4 lymphocytes irrespective of
how it is induced, that is, by destruction of the T4 cells or by a
phenotypic change, and of its cause, is neither necessary nor sufficient
for the appearance of KS and OI including PCP, that is, of the clinical
syndrome.

Problems with the Western Blot Antibody Test
*
The Western Blot has ten "bands", all of which have a protein or antigen
that is supposedly only produced by HIV. The ELISA test also uses these
"HIV proteins", but as a mixture so only one band needs to be used. The
patient's serum is run separately through all ten bands of the Western
Blot to see how it will react with each one individually. When the serum
reacts with a protein in a given band it is considered to mean that the
patient's serum contains antibodies to that particular protein. Not all
ten bands have to be positive in order for a person to be diagnosed
HIV-positive however, and the combinations of reactive bands needed for a
positive result vary greatly from country to country. This fact alone
shows how arbitrary the tests are, since a person diagnosed HIV-positive
in one country may be considered "indeterminate" in another.
*
The following quote from Proffitt et al. describes the inconsistent
guidelines for the reading of this test (Proffitt 1993):
*
“Indeed, not even the interpretation guidelines in the brochures of each
FDA-licensed manufacturer of HIV Western Blots are the same. However, the
majority of the laboratories have accepted the recommendations of the
ASTPHLD. Following those recommendations, a negative Western Blot would
have no bands, a positive would have at least two of the key bands, and an
indeterminate would have a single band or a combination that does not fit
the interpretation of positive.” (page 208)
*
This comment hardly inspires confidence that interpretations of results
are based on sound scientific principles. It also explains why different
countries have widely varying criteria for when a test is "positive" and
when it is "indeterminate". The most disturbing evidence they cite,
however, is the rate of indeterminates that appear for Western Blots in
healthy blood donors as discussed previously. An indeterminate occurs when
an insufficient number of bands come up positive or when the combination
"does not fit the interpretation of positive". One would expect, since all
of the bands contain proteins that are supposedly specific to HIV that
indeterminate results would be quite rare, but this is hardly the case.
*
Problems may be encountered when an HIV Western Blot is done on someone at
no identifiable risk of infection. For example, recent studies of blood
donors in whom no risk for HIV infection could be ascertained, who were
nonreactive on the ELISA, and for whom all other tests for HIV were
negative, revealed that 20% to 40% might have an indeterminate Western
Blot. (page 209) This means that any one of us, if given a Western Blot
HIV antibody test, will have a 20% to 40% chance of having our serum react
with proteins that are supposedly specific to HIV! As mentioned before,
such a high rate of indeterminates on a test that supposedly determines
life or death issues is outrageous in my opinion, and yet Proffitt et al.
do not question its accuracy in any way.
*
Given the high rate of indeterminate results on the Western Blot, it is
reasonable to wonder how the extremely high specificity claimed for this
test can possibly be true. It is claimed is that only 1 in 20,000 tests
will give a false positive. An article from 1995 that also supports the
use of these tests places these two seemingly irreconcilable claims in the
very same sentence:
*
“Thus, incidences of inaccurate results [on the Western Blot] vary from a
false positive rate of 1 in 20,000 to indeterminate results in 20% to 40%
of cases in which the ELISA test was serum negative.” (Cordes 1995, page
185)
*
The only conclusions that Proffitt et al. draw from this extremely high
false indeterminate rate is that the Western Blot should not be used as an
initial screening test, and the only potential harm mentioned is that "the
anxiety an indeterminate result creates in a test subject is
understandably intense." (Proffitt 1993, page209).
*
If an indeterminate result creates "intense" anxiety, a result considered
to be a true positive will create levels of stress and anxiety that are
many times more intense. I have called the fear and social isolation
caused by a positive HIV antibody test result "psychological terrorism"
because of how devastating it can be, and yet the decision about what is
"true", "false" or "indeterminate" does not appear to be based in any well
controlled experiments and appears to ignore many conflicting results.
*
The arbitrary nature of the Western Blot has been analyzed in detail by
Papadopulos-Eleopulos et al. (1993) who document that all of the proteins
used in the Western Blot, which are supposedly specific to HIV, have been
commonly found in people who are HIV-negative on the other HIV tests. They
also point out that HIV was never isolated so there is no way to know if
these proteins are from HIV or from other cells and viruses. Before
analyzing their work, however, here is a quote from a team of researchers
who reported a number of false positive results on the Western Blot tests:

*
“Our results document a fourth source of false positive HIV-1 Western Blot
results which is the reproducible but nonspecific reactivity [to proteins
from HIV]... Preliminary studies suggest that the basis for this cross
reactivity with HIV-1 gp 41 proteins may be infection by paramyxoviruses,
carbohydrate antibodies, or autoantibodies against cellular proteins.
(Sayre et al., 1996, page 48-49).
*
The authors also looked at rates of these types of false positives among
all tests performed on blood donors in the U.S. and concluded that 1992
had the highest rates to date with 52 out of 683, or 8% of Western Blot
positives on donated blood actually being false positives.
*
The quote above from Sayre et al. mentions false positives due to
reactions with the "gp 41 proteins" which include gp 41 and gp 120/160.
However, there have been problems with the proteins in all the other bands
used in the Western Blot as well. It has been shown in a number of studies
that none of the ten proteins are actually specific to HIV. "Gp" stands
for "glycoprotein", which is a protein with some sugar molecules attached
to it, and the number after the letters represents the molecular weight of
the protein, in kilodaltons. Glycoproteins of all shapes and sizes are
extremely common components of cells in both plants and animals. (These
proteins are sometimes referred to with only a “p”, i.e. “p41” and
“p120/160” instead of “gp”.)
*
The research calling into question whether any of the "HIV proteins" is
really specific to HIV is presented in detail in an article published in
Bio/Technology, by Papadopulos-Eleopulos et al., entitled "Is a Positive
Western Blot Proof of HIV Infection?" (Papadopulos-Eleopulos et al.1993).
The authors point out that even the original papers by HIV co-discoverer
Luc Montagnier found gp41 to occur in normal cells which were not infected
by HIV, and that Montagnier's group concluded that gp41 "may be due to
contamination of the virus by cellular actin which was present ... in all
the cell extracts" (Barre-Sinoussi et al. 1983). Actin is an extremely
common protein that is present in all cells, including bacteria and
viruses. The gp 120/160 protein was shown in 1989 to actually be several
gp 41 proteins hooked together ("oligomers" of gp 41), so it is equally
non-specific. This was reported by Pinter et al in 1989 in the Journal of
Virology in an article entitled, "Oligomeric Structure of gp41, the
Transmembrane Protein of HIV-1".
*
Another protein, gp24, is of special significance because it is often used
alone as a test to claim the presence of HIV and gp24 testing is commonly
done in newborn children where the ELISA and Western Blots are thought to
give false positives due to antibodies passed on by an HIV positive
mother. Additionally, when HIV is "cultured", it is the finding of gp24
that is used to say HIV has been found. In other words, the way they test
for HIV is to test for gp24. Thus, this glycoprotein has special
importance, and one would expect that it would be extremely rare to find
it in people considered HIV negative. As Papadopulos-Eleopulos et al. put
it:
*
"Detection of p24 is currently believed to be synonymous with HIV
isolation and viremia. However, ... Gallo and his colleagues have
repeatedly stated that the p24's of HTLV-1 (a different retrovirus) and
HIV cross-react." (Papadopulos-Eleopulos et al.1993 page 697, Wong-Staal &
Gallo 1985).
*
Papadopulos-Eleopulos et al. continue with further examples showing how
incredibly common it is to find gp 24 and antibodies to gp 24 in people
who are considered HIV-negative:
*
“Genesca et al (1989) conducted Western Blot assays in 100 ELISA-negative
samples of healthy blood donors. 20 were found to have positive bands
which ... were considered indeterminate Western Blots, with p24 being the
predominant band (70% of cases). Among the recipients of Western Blot
indeterminate blood, 36% were Western Blot indeterminate 6 months after
transfusion, but so were 42% of individuals who received Western
Blot-negative blood samples. Both donors and recipients of blood remained
healthy. They concluded that Western Blot indeterminate patterns "are
exceedingly common in randomly selected donors and recipients and such
patterns do not correlate with the presence of HIV-1 or the transmission
of HIV-1... Most such reactions represent false positives."
*
Antibodies to gp24 have been detected in 1 out of 150 healthy,
ELISA-negative individuals, 13% of randomly selected otherwise healthy
patients with generalized warts, 24% of patients with cutaneous T-cell
lymphoma, and 41% of patients with multiple sclerosis (Ranki et al. 1988).
Conversely, the p24 antigen is not found in all HIV positive or even AIDS
patients. In one study of patients at various stages from asymptomatic
(HIV positive) to AIDS, p24 was detected in only 24% (Delord et al.
1991).
*
Here we have researchers discussing the "exceedingly common" occurrence of
Western Blot indeterminate results and deciding that they represent false
positives because the ELISA is negative. As noted previously, ELISA
positives are considered to be false when the Western Blot was negative.
The incredible reliance of patients, doctors, and scientists on tests with
such obvious inconsistencies is a cause for alarm, and yet it appears that
the only people sounding the alarm are not being heard, or at least not
being listened to. The rest of the article by Papadopulos-Eleopulos et al.
goes on to discuss similar findings with the rest of the Western Blot "HIV
proteins" and concludes with a relatively conservative call for
reappraisal:
*
“We conclude that the use of the HIV antibody tests as a diagnostic and
epidemiological tool for HIV infection needs to be reappraised.” (page
696)
Of even greater concern than the existence of these problems is the fact
that no one in the conventional medical and scientific establishment seems
to be asking questions about them.
*
Problems with the Viral Load Test
*
Two papers published in 1995 in the journal Nature appeared to resolve the
dilemma of either not being able to find any actual HIV particles, or
finding only extremely small quantities of HIV, in people diagnosed
HIV-positive (Ho 1995, Wei 1995). These researchers used a new genetic
detection system called "quantitative PCR", which relies on a complex
mathematical formula to quantify the amount of virus in people's blood.
This abstract quantification system is what is still used today to find
what is called a person's "viral load", and has become a major method used
by clinicians to determine the health status of people diagnosed
HIV-positive. Contrary to what most people believe, however, PCR does not
directly detect any intact viral particles, but only tiny fragments of
what is thought to be HIV's genetic material. Thus, "viral load" is not
determined by counting even one intact particle of HIV, but rather by
using a complex mathematical system of estimation. This quantification
system has serious problems that have been largely ignored in spite of
being clearly reported in the medical literature, and yet it has become
the primary marker of health both in research as well as in treatment
decisions with people diagnosed HIV positive.
*
How many HIV particles does "viral load" really represent?
*
Viruses can only cause damage if they are infectious. They cause ill
health by infecting cells and then causing cell death. Researchers
attempting to see what portion of the huge numbers of HIV reported by
quantitative PCR represent active, infectious viruses, have found that as
few as 1 in 10 million of the “HIV” reported are actually infectious. They
determine this by "culturing" the virus, which usually means looking for
surrogate markers of HIV like gp 24. As outlined previously, these
proteins are actually quite non-specific and are often found in people who
are HIV-negative.
*
A virus that cannot infect another cell is essentially sterile since it
cannot harm any cells if it cannot infect them. Here are some comments on
the results from one major study published in Science in which researchers
found that the vast majority of "viral particles" found by viral
load/quantitative PCR were non-infectious:
“Circulating levels of plasma virus determined by [quantitative] PCR
correlated with, but exceeded by an average of 60,000-fold, numbers of
infectious HIV-1 that were determined by quantitative culture of identical
portions of plasma... Total virions have been reported [in other studies]
to exceed culturable infectious units by factors of 1,000 to 10,000,000,
ratios similar to those we observed in plasma.” (Piatak et al., 1993, page
1752)
*
In other words, these researchers estimated that only about 1 in 60,000
"virions" found using "quantitative" PCR were actually infectious, and
that other studies have found even more dismal results. Because they use
the presence of gp24 which is a non-specific protein found in 41% of
patients with multiple sclerosis (Ranki et al. 1988) to determine if a
cell has become infected, even their estimate of 1 in 60,000 is probably
exaggerated.
*
Even using a non-specific marker like gp24, these researchers were not
able to culture any virus at all in more than half (35 of 66) patients.
This means that people with no infectious virus at all had "viral loads"
as high as 815,000 "copies per milliliter"! The study subjects had all
tested positive on the ELISA and Western Blot antibody tests, the two
tests currently used to diagnose people as being "HIV-infected". They all
had extremely high "viral loads", and yet the majority of them had no
"culturable infectious units" of HIV. Results like these bring up some
obvious questions about what proof exists that testing positive on
antibody tests means that a person had an active infection. Unfortunately,
in the world of HIV science, no one seems to question these tests.
Instead, articles commonly quote amazing levels of specificity and
sensitivity.
*
This difficulty in finding active HIV particles is not surprising to those
familiar with the literature on this topic, since similar results have
been found by many researchers who have tried to confirm the presence of
HIV in people's blood (Chiodi 1988, Gallo 1984, Learmont 1992, Popovic
1984, Sarngadharan 1984, Schupbach 1984). Based on results like these, the
abstract system used by quantitative PCR technology in which tiny bits of
genetic material are amplified by a complex set of mathematical equations
into frighteningly large numbers is highly questionable. Most people
diagnosed HIV positive, even with high viral loads, may have noinfectious
virus in them at all. As will be discussed in the next section, many
people who test negative on both the ELISA and Western Blot have
substantial viral loads when tested using "quantitative PCR". This brings
up the question of whether PCR is capable of mistaking tiny bits of a
person's own genetic material for genetic material of HIV. Since the human
genome has about 3 billion base pairs while that of HIV has only about
10,000, and PCR only looks for about 3% of HIV's genetic material, about
300 base pairs, it appears likely that some of the 3 billion base pairs in
the human genome could accidentally be attributed to HIV.
*
As mentioned before, "viral load" has become the only measure of alleged
health in clinical trials of new drugs. News reports about people "doing
well" on the new anti-retroviral cocktails often speak about people whose
"disease is controlled" on the drugs, or whose "disease came roaring back"
after stopping the drugs. What they are referring to, however, is not
clinical health at all. Careful reading of such articles reveals that the
person in question often feels much better when they discontinue the drugs
because of the numerous toxic effects suffered while taking them. The
description of the disease "roaring back" is based entirely on the fact
that their "viral loads" have risen, even though they may be feeling much
better and have no clinical symptoms of illness.
*
As often occurs in studies that fundamentally challenge HIV science like
Piatak et al, the authors appear unphased by their results and focus
completely in the discussion section of their paper on other aspects of
their study that fit better with conventional views about what it means to
be "HIV-positive" and to have a high "viral load". They do not even
mention in their discussion that the majority of their subjects had no
infectious viral particles. While it is of questionable significance to
have such high "viral loads" if only a tiny minority, or none of the
particles is actually infectious, it can still be terrifying to be told
that one has several million copies of HIV in every milliliter of blood.
This type of news has a powerful symbolic meaning to clinicians and
patients, which may result in profound immunosuppression whether HIV is
causing damage or not.
*

HIV and the T4 cells

Using MCA for serial measurement of CD4 and CD8 expressing lymphocytes in
mitogenically stimulated HIV infected cultures, it has been shown that in
cultures prepared such that the majority (>95%) of lymphocytes are
purified T4 cells, there is a progressive disappearance of CD4 expressing
cells. This observation was interpreted by Gallo and others "that HTLV-III
has a cytopathic effect on OKT4-positive (OKT4+) cells" (Fisher et al.,
1985). However, according to Klatzmann, Montagnier and other French
researchers "this phenomenon could not be related to the cytopathic
effect" of HIV but is "probably due to either modulation of T4 molecules
at the cell membrane or steric hindrance of antibody-binding sites"
(Klatzmann et al., 1984a Klatzmann et al., 1984b). That is, the decrease
in T4 cells is not due to destruction of cells but due to a decrease in
MCA binding to their surface. Nevertheless, the above data were
interpreted as evidence for selective infection and killing of T4 cells by
HIV, and together with the fact that "we knew of no agents, aside from a
family of human T- lymphotropic retroviruses that we had discovered three
years earlier and named human T-cell leukaemia (lymphotropic) virus
(HTLV), that demonstrated such tropism to a subset of lymphocytes", was
presented as one of two arguments in support of the HIV hypothesis of AIDS
(Gallo et al., 1985). (The other argument was based on the perceptions
that AIDS was a new disease and the epidemiology was consistent with an
infectious cause).

However:

(a) HIV cultures/co-cultures are stimulated with such oxidising agents as
PHA, ConA, radiation, PMA, polybrene and IL-2;

(b) these agents at relatively low concentration can induce decrease in
CD4 expressing cells, in the absence of HIV (Acres et al., 1986; Hoxie et
al., 1986; Zagury et al., 1986; Scharff et al., 1988), without killing T4
cells.

(c ) in 1986, Zagury, Gallo and their associates (Zagury et al., 1986),
prepared T-cell cultures (which contained 34% CD4+ cells), from normal
donors. Cultures were stimulated with PHA and were (i) "infected" with
HIV; (ii) left uninfected. Control cultures remained both unstimulated and
uninfected. After 2 days of culture, the proportion of CD4+ cells in the
stimulated-uninfected and stimulated-infected cultures was 28% and 30%
respectively, while at 6 days the number was 10% and 3%; the controls not
changing significantly.

Thus, HIV is not necessary for the disappearance of CD4 expressing cells,
as measured by the use of MCA in "HIV infected" stimulated cultures. The
stimulants can induce the effect in the absence of "HIV". Furthermore, the
decrease in T4 cells may not be due to destruction of T4 cells but to a
decrease in the number of cells binding MCA.

Even if the in vitro evidence shows that HIV is a cytopathic retrovirus
and that it preferentially infects and kills T4 lymphocytes, evidence must
exist that the same effect takes place in vivo, that is, patients infected
with HIV have diminished numbers of T4 cells which is caused by
preferential infection and killing of these cells by HIV.

Following the frequent diagnosis of KS, PCP and other opportunistic
infections (OI) in gay men and intravenous (IV) drug users, it was
realised, when T lymphocytes of these patients were reacted with MCA to
the CD4 antigen, the number of CD4 antigen bearing cells is diminished.
This led to a diagnosis of "acquired immune deficiency" defined as a
decrease in T4 cell number, which was thought then and now to be due to
the death of T4 cells. This finding, together with the then known fact
that patients who were treated with the so called immunosuppressive drugs
or who suffered from "immunosuppressive illness" had relatively high
frequencies of KS and OI, led to the conclusion that the high frequencies
of these diseases in gay men, IV users as well as haemophiliacs amongst
others, were the direct result of suppressed cellular immunity
(immunosuppression) defined by diminished numbers of T4 helper cells
(cell-mediated immunodeficiency). In 1982, the Center for Disease Control
(CDC) defined a case of AIDS as "illnesses in a person who 1) has either
biopsy-proven KS or biopsy-or culture-proven life-threatening
opportunistic infection, 2) is under age 60, and 3) has no history of
either immunosuppressive underlying illness or immunosuppressive therapy"
(CDC, 1982). The claim by Gallo and his colleagues in 1984 that AIDS is
caused by HIV led the CDC to redefine AIDS.

In 1985 the CDC defined AIDS as: "I. one or more of the opportunistic
diseases listed below (diagnosed by methods considered reliable) that are
at least moderately indicative of underlying cellular immunodeficiency;
and II. absence of all known underlying causes of cellular
immunodeficiency (other than LAV/HTLV-III infection) and absence of all
other causes of reduced resistance reported to be associated with at least
one of those opportunistic diseases.

Despite having all the above, patients are excluded as AIDS cases if they
have negative result(s) on testing for serum antibody to LAV/HTLV-III, do
not have a positive culture for LAV/HTLV-III, and have both a normal or
high number of T- helper (OKT4 or LEU3) lymphocytes and a normal or high
ratio of T-helper to T-suppressor (OKT8 or LEU2) lymphocytes. In the
absence of test results, patients satisfying all other criteria in this
definition are included as cases" (WHO, 1986).

This definition presupposes that proof exists or can be obtained that HIV
is the sole cause of the acquired immune deficiency (decreased T4) which,
in turn, leads to the appearance of the clinical syndrome. Such a proof
can only be obtained by the administration of PURE HIV to healthy humans
or, as Montagnier (Vilmer et al., 1984) pointed out in 1984, "Definite
evidence will require an animal model in which such viruses could induce a
disease similar to AIDS". At present no animal AIDS model exists and of
course it is not ethical to administer HIV, pure or otherwise, to humans
(Papadopulos-Eleopulos et al., 1993a). In the absence of the above one
must, at the very least, have (indirect) evidence that:

(a) in HIV positive individuals, at least by the time diseases attributed
to HIV infection such as persistent generalised lymphadenopathy (PGL) and
AIDS-related complex (ARC) have appeared, there is an abnormally low T4
cell number;

(b) in patients defined as AIDS cases the decrease in T4 cells follows and
does not precede "HIV infection", as evidenced by a positive HIV antibody
test;

(c ) patients before, during or after seroconversion have not been exposed
to any agents known to cause immunosuppression;

(d) following seroconversion there must be a steady decrease in T4 cell
numbers.

However, three years after seroconversion the majority of HIV positive
individuals continue to have normal T4 cell counts (Detels et al., 1988).
Even in the presence of PGL and other "constitutional symptoms of
HIV-related diseases", a significant number of patients continue to have
normal T4 cell numbers (T4/T8 ratio). In some individuals, seroconversion
is followed by an increase, not a decrease in T4 cells (Detels et al.,
1988; Natoli et al., 1993).

When AIDS was first diagnosed in gay men and IV drug users, but before the
discovery of HIV, epidemiological data, some of which appeared in the
Morbidity and Mortality Weekly Reports published by the CDC, rapidly
accumulated which showed that in the 1970's, individuals from the AIDS
risk groups suffered from many infectious and non-infectious diseases
unrelated to AIDS. Data was recently presented from the Multicenter AIDS
Cohort Study (Hoover et al., 1993) (MACS) which shows that HIV
seropositive gay men "at least 1.67-3.67 years prior to a clinical
diagnosis of AIDS", as well as HIV seronegative gay men, although the
frequency in the latter is lower, suffer from a wide variety of complaints
including fatigue, shortness of breath, night sweats, rash, cough,
diarrhoea, headaches, thrush, skin discolouration, fever, weight loss,
sore throat, depression, anaemia and sexually transmitted diseases.
Evidence which existed at the beginning of the AIDS era, or which has
accumulated since, shows that some of the diseases which occurred in these
individuals, or the agents which caused them, including Epstein-Barr virus
and CMV, are immunosuppressive (Papadopulos-Eleopulos, 1988). Many of the
agents used in treatment, including corticosteroids and some antibiotics,
as well as the recreational drugs used by both gay men and drug users, are
also known to be immunosuppressive. From the start of the epidemic, the
CDC was aware that approximately 50% of gay men used nasal cocaine and
about the same proportion smoked marijuana. Nitrite use was considered
practically ubiquitous.

That the immunosuppression found in AIDS patients is not caused by HIV is
indicated by the fact that individuals from the AIDS risk groups may have
low T4 cell numbers (T4/T8 ratio), even in the presence of a persistently
negative HIV antibody test (Drew et al., 1985; Novick et al., 1986;
Donahoe et al., 1987; Detels et al., 1988). Although one such study showed
"reduced proliferative response to the T cell mitogen PHA in AIDS...PHA
responses in symptomless HIV infection, with or without lymphadenopathy,
were also significantly reduced compared to heterosexual controls. However
seronegative homosexuals had similarly reduced PHA responses. Thus, in
symptomless infection, HIV does not appear to cause more impairment than
seen in their uninfected peers...Our findings re-emphasise the importance
of using seronegative peer group controls in studies on HIV infection"
(Rogers et al., 1989).

In considering the data from haemophiliacs, a group of British
researchers, including the well known retrovirologist Robin Weiss,
concluded in 1985: "We have thus been able to compare lymphocyte subset
data before and after infection with HTLV- III. It is commonly assumed
that the reduction in T-helper- cell numbers is a result of the HTLV-III
virus being tropic for T-helper-cells. Our finding in this study that
T-helper- cell numbers and the helper/suppressor ratio did not change
after infection supports our previous conclusion that the abnormal
T-lymphocyte subsets are a result of the intravenous infusion of factor
VIII concentrates per se, not HTLV-III infection" (Ludlam et al., 1985).

In relation to patients with haemophilia A, von Willebrand's disease and
"hypertransfused patients with sickle cell anaemia" Kessler et al found
that: "Repeated exposure to many blood products can be associated with
development of T4/T8 abnormalities" including "significantly reduced mean
T4/T8 ratio compared with age and sex-matched controls" (Kessler et al.,
1983). In 1984, Tsoukas et al observed that amongst a group of 33
asymptomatic haemophiliacs receiving factor VIII concentrates, 66% were
immunodeficient "but only half were seropositive for HTLV-III", while
"anti-HTLV-III antibodies were also found in the asymptomatic subjects
with normal immune function". They summarised their findings as follows:
"These data suggest that another factor (or factors) instead of, or in
addition to, exposure to HTLV-III is required for the development of
immune dysfunction in haemophiliacs" (Tsoukas et al., 1984).

By 1986 researchers from the CDC concluded: "Haemophiliacs with immune
abnormalities may not necessarily be infected with HTLV-III/LAV, since
factor concentrate itself may be immunosuppressive even when produced from
a population of donors not at risk for AIDS" (Jason et al., 1986) (factor
concentrate=factor VIII). In 1985 Montagnier (Montagnier, 1985) wrote:
"This [clinical AID] syndrome occurs in a minority of infected persons,
who generally have in common a past of antigenic stimulation and of immune
depression before LAV infection", that is, Montagnier recognised that in
the AIDS risk groups, AID appears before "HIV infection" [LAV=HIV]. A
recent study of IV drug users in New York (Des Jarlais et al., 1993)
showed that "The relative risk for seroconversion among subjects with one
or more CD4 count <500 cells/uL compared with HIV-negative subjects with
all counts >500 cells/uL was 4.53". A similar study in Italy (Nicolosi et
al., 1990) showed that "low number of T4 cells was the highest risk factor
for HIV infection", that is, decrease in T4 cells is a risk factor for
seroconversion and not vice versa. The observations that T4 decrease
precedes a positive antibody test ("HIV infection"), is additional
(Papadopulos-Eleopulos et al., 1993a) evidence that factors other than HIV
lead to both T4 decrease and positive "HIV" antibody tests.

Thus gay men, IV users and haemophiliacs, have "known underlying causes of
cellular immunodeficiency (other than LAV/HTLV-III infection)", and
therefore, according to the 1985 CDC AIDS definition, these individuals
cannot be AIDS cases. The finding in individuals belonging to the above
groups of a decreased T4 cell number and decreased T4/T8 ratio, even if
due to killing of T4 cells and not to "modulation of T4 molecules at the
cell membrane or steric hindrance of antibody-binding sites", cannot be
interpreted as being caused by HIV. Nonetheless, from 1981 to the present,
gay men, IV users and haemophiliacs form the vast majority of AIDS cases.


From the beginning, it was realised that in AIDS patients the decrease in
T4 lymphocytes is accompanied by an increase in T8 lymphocytes while the
total T cell population remains relatively constant. This has recently
been confirmed by Margolick et al who showed that the decline in T4 cells
in HIV positive individuals is accompanied by a T8 increase "with kinetics
that mirrored the loss of CD4+ cells, resulting in a CD8 polarization"
(Margolick et al., 1993; Stanley & Fauci, 1993).

This finding has been neglected until recently when a theory has been put
forward to explain how infection of even a small proportion of T4 cells,
(perhaps 1/1000) can have this effect. This theory states that "loss of
either CD4+ or CD8+ T cells is detected by the immune system only as a
decrease in CD3+ T cells. The compensatory response to such a selective
decrease, then, is to generate both CD4+ and CD8+ T cells in order to
bring the total CD3+ T cells back to a normal level. The consequence of
this nonselective T cell replacement after a selective depletion of one T
cell subset would be an alteration in the CD4 to CD8 ratio after
normalization of the total T cell count with a polarization toward the
subset that had not been initially depleted...repeated events of selective
CD4+ T-cell killing will result in higher and higher CD8+ T- cell count
and lower and lower CD4+ T-cell count" (Adleman & Wofsy, 1993; Margolick
et al., 1993; Stanley & Fauci, 1993)

However, a brief look at the history of the discovery of the T4 and T8
cells and the presently available data show that the above theory may not
be valid.

In 1974, a group of researchers from the National Cancer Institute USA
observed that when normal lymphocytes were cultured with T-cells from
hypogammaglobulinaemic patients in the presence of PWM, the synthesis of
immunoglobulin (antibodies) by the normal lymphocytes was depressed by 84%
to 100%. They put forward the hypothesis "that patients with common
variable hypogammaglobulinemia have circulating suppressor T lymphocytes
that inhibit B-lymphocyte maturation and immunoglobulin synthesis"
(Waldman et al., 1974). Subsequently, it was shown that ConA stimulated T
cells from healthy animals "can under appropriate circumstances perform
helper, suppressor, and killer functions" (Jandinski et al., 1976). By
1977 many studies of the cellular basis of the immune response had
indicated that T cells have both suppressive and helper activities and it
was concluded that "these activities are specialized functions of distinct
subclasses of T cells", which could be distinguished by cell- surface
components thought to be specific to each subclass (Cantor & Boyse, 1977).
In the late 1970s the discrimination and separation of these two
subclasses were facilitated by the development of MCA to cell-surface
antigens considered specific for each subclass, the subclasses being given
the name T4-helper and T8-suppressor cells (Reinherz et al., 1979). By
1980 it was generally accepted that:

(a) in humans the CD4 antigen and the CD8 antigen are expressed on helper
and suppressor T cell subsets respectively. "Each T-cell subclass has a
unique set of biological properties and immunologic functions" (Cantor &
Boyse, 1977). "T4+ T cells provide helper function for optimal development
of cytotoxicity in cell-mediated lympholysis...In addition, the T4+ subset
produces a variety of helper factors that induce B cells to secrete
immunoglobulin and all lymphocyte subpopulations (T,B and null) to
proliferate". The T8 subset "suppresses the proliferative response of
other T cells and B-cell immunoglobulin production and secretion"
(Reinherz et al., 1981).

(b) "cells of these two subclasses do not give rise to one another...they
represent products of separate subclasses of thymus dependent maturation",
that is, "although both T4+ and T5+ subsets arise from a common progenitor
cell within the thymus, they diverge during ontogeny and result in
separate subsets" [T5=T8].

(c ) "stimulation of T cells by conventional antigens, histocompatibility
antigens and mitogens results in the formation of suppressor T cells"
(Cantor & Boyse, 1977;