By Vladimir Koliadin
April 1998 (Revised June 1999)
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Introduction
In 1993, the widely accepted ideas that a positive test for HIV-antibodies is specific (i.e. means HIV-infection) and that HIV exists as an exogenous retrovirus were challenged by Papadopulos-Eleopulos et al. (Perth Group) [1]. Then these views were developed by the same [2] and other authors [3,4]. Neither experimental nor even logical arguments were advanced by mainstream AIDS-scientists to disprove the central points of the Perth Group [1,2] *. At present, it is still accepted in mainstream AIDS-science that existence of HIV and high specificity of HIV-antibody tests are ultimately proven scientific facts. Besides conformity of thinking and vested interests, this belief is maintained due to the absence of clear-cut alternative explanations for the phenomena which are thought to prove the HIV-causes-AIDS theory. Some important questions have not been answered. If HIV does not exist, what causes a positive test for HIV-antibodies? Why are almost all AIDS-patients seropositive while almost all healthy individuals are not? Why is the positive test strongly associated with high mortality and susceptibility to opportunistic infections?
At the heart of any HIV-antibody test are the so called HIV-proteins. These proteins are produced by cell-cultures of human lymphocytes. According to the mainstream AIDS-science, these proteins belong to a new retrovirus HIV, by which these cell-lines are presumably infected. HIV-skeptics say that these proteins are of endogenous (intracellular) nature [1]. Following the facts and basic principles of immunochemistry, the only conclusion which may be drawn from a positive test for HIV-antibodies is that some immunoglobulins in the tested blood-serum have bound to these "HIV-proteins". This is the case for both ELISA and Western Blot (WB) tests, as well as for any other immunochemical test. The point of disagreement is how to interpret such binding. Mainstream science insists that such binding is due to specific antibodies, produced by the immune system after it comes in contact with HIV. The Perth Group [1,2] explain this binding by cross-reactions between "HIV-antigens" and antibodies to other non-HIV antigens, to which AIDS- patients and individuals from high-risk groups are exposed. Such cross-reactions are well known to occur when different antigens share common parts ("antigen determinants"). In this case, antibodies to one such antigen are capable of binding selectively to another antigen with the same antigenic determinants. Nevertheless, the cross-reactivity hypothesis suffers from one problem: how to explain that almost all AIDS-patients and many people in high-risk groups have been exposed to some antigens bearing common determinants only with "HIV-antigens"? Why almost everyone beyond the risk- groups have not been exposed to such antigens, although anyone in the course of his/her life has been exposed to many antigens (vaccinations, infections, etc.)?
1. Why HIV-antibody tests are thought to be specific
In the middle of the1980s, it was shown experimentally that a test for HIV-antibodies is positive in a great proportion of patients with a diagnosis of AIDS or pre-AIDS, while it is negative in almost all perfectly healthy individuals. It should be noted that AIDS-diagnosis in these patients was established from clinical symptoms, not from the HIV-test itself. This undermines the "circular definition" argument advanced by some AIDS-dissidents. Moreover, such studies were carried out according to a blind and randomized protocol [9]. This gave great credibility to the HIV-causes-AIDS viewpoint. Do such studies actually prove that HIV- positivity is specific to AIDS? Even though it may seem "self-evident" at first sight, it is not so. An important principle of evidence-based science was obviously violated in these studies: the control group was not matched to the AIDS group - perfectly healthy individuals were used as controls [1].
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Among other studies carried out with large number of individuals (applicants for US military service) specificity of HIV-tests has been reported as high as 1 false positive reaction in more than 135,000 [5]. Nevertheless, these studies have nothing to do with proofs of existence of HIV or specificity of HIV-antibody tests because only WB test systems were used as the "gold standard" of HIV. All these studies demonstrated is that results provided by some ELISA systems in multistep testing algorithms are well compatible with results of WB tests, at least in a population with a predicted very low prevalence of HIV-seropositivity. The unknown specificity of the "confirmatory" WB-tests themselves was not addressed in these studies.
2. Non-specific immunoglobulins as the cause of HIV-seropositivity
The B-lymphocytes (a part of the immune system) normally respond to foreign substances (named "antigens") by increased production of special proteins - immunoglobulins. Some of these immunoglobulins are capable of specific binding to the antigen - that is, they bind strongly to the antigen but not to other substances. Such immunoglobulins are usually named "antibodies". Other immunoglobulins, which are capable to bind to a wide range of antigens, are named "non-specific immunoglobulins". Many authors name all immunoglobulins "antibodies"; to discriminate between the two types they use the terms "specific antibodies" and "non-specific antibodies" (or "normal antibodies"). The ability of (specific) antibodies to bind only to the antigen which induced production of these antibodies plays a very important role in biomedical science and serological testing.
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The problem of non-specific immunoglobulins is exacerbated in the tests which are based on "sandwich" principle (as in ELISA and WB). In these test-systems, the antigen (e.g. "HIV- antigen") is attached to a surface and forms the first layer in the "sandwich". After exposure to the tested serum, immunoglobulins from the serum bind to the antigen and form the second layer in the "sandwich". To detect these immunoglobulins and estimate their quantity the two-layer sandwich is subject to one more procedure - exposure to antibodies against human immunoglobulins (which are obtained from laboratory animals immunized by human immunoglobulins). These animal antibodies bind to the human immunoglobulins and form the third layer of the sandwich. Only the amount of the animal antibodies bound to human immunoglobulins, not the quantity of the human immunoglobulins themselves, is being measured in test-systems of this sort [9]. It is tacitly postulated that affinity (ability to bind) of the animal antibodies to human immunoglobulins is about the same for all individuals and, hence, the amount of the animal antibodies bound is simply proportional to the amount of human immunoglobulins. But this is not the case if non-specific immunoglobulins from some individuals are capable of binding more strongly to various substances than immunoglobulins from healthy controls. Let us say, for example, that non-specific affinity of non-specific immunoglobulins increased 3 times in respect to various proteins, including both "HIV-antigens" and animal antibodies. Then, the number of molecules of human non-specific immunoglobulins bound per one molecule of the antigen is 3 times higher. After exposure to animal antibodies, 3 times higher number of molecules of the animal antibodies will be bound per one molecule of human immunoglobulins. Thus, the total amount of animal antibodies will be 9 times (3 multiplied by 3) higher, not 3 times. Hence, even a moderate increase in non- specific affinity of immunoglobulins may lead to radical increase in the titers and, hence, to HIV-seropositivity.
3. What increases the levels of non-specific immunoglobulins
Given that elevated levels of non-specific immunoglobulins and their increased affinity may lead to positive tests for "HIV-antibodies" it is reasonable to consider the causes of such conditions. It is widely accepted that hypergammaglobulinemia (which is typical to AIDS and many other conditions) results from polyclonal activation of B-lymphocytes caused by intensive stimulation by multiple foreign antigens. Individuals in groups with high risk of AIDS are exposed with abnormal frequency to such multiple antigens [1]: multiple infections, including STD and AIDS-defining opportunistic infections, anal reception of semen, contaminants of injected recreational drugs, foreign blood received either in course of sharing syringes for injection of such drugs or as transfusions, contaminants of the blood factors received by hemophiliacs as well as these factors themselves. Thus, the significantly higher frequency of positive tests for "HIV-antibodies" observed in the groups with high risk of AIDS is highly likely to be nothing but an indicator of such over-stimulation by multiple foreign antigens and, in many cases, an indicator of some diseases. Nevertheless, there are no factual reasons to consider the antigen overload itself as a life-threatening factor.
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Besides the role of foreign antigens, there is another plausible hypothesis advanced; it holds that both typical signs of AIDS - hyperactivation of B-cells and T4-lymphocytopenia - are intrinsic features of the classical stress-syndrome [11]. Stress-syndrome is a highly non-specific reaction of the organism to various adverse factors: diseases, intoxication, psychological trauma, etc. This reaction is mediated by elevated concentrations of corticosteroids ("stress-hormones"), and it may be induced by direct injection of corticosteroids. (Incidentally, corticosteroids are frequently used to treat inflammatory conditions in AIDS-patients.) If this hypothesis is combined with the aforementioned one (that hyperactivation of B-cells results in increased affinity of non-specific immunoglobulins), it provides a coherent explanation of why people with severe opportunistic infections (named AIDS) usually demonstrate T4-lymphocytopenia and HIV-seropositivity.
4. HIV and mortality in Africa: another look at the facts
In a study conducted in a rural population of Uganda (Lancet 1994, 343, 1021-23), about 10,000 individuals were tested for "HIV-antibodies". In those aged 13-44 years, 9.6% were found HIV- seropositive. During follow up, mortality was estimated as 96/1000 man-years (=96 persons out of 1000 in 1 year) in the HIV-positive group, and as only 1.4/1000 m.-y. in the HIV-negative group. Thus, mortality in HIV-seropositives was 60 times higher than in their HIV-negative counterparts. At first sight, these results seem to be a reliable proof for a causal role of HIV in AIDS, specificity of HIV-tests, and reality of HIV. For this reasons these results are frequently referred to by proponents of the HIV-AIDS theory (see for example [12,13]).
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Proponents of the HIV-AIDS theory [12] insist that the 9.3/1000 m-y mortality in the 13-44 age group at large is significantly higher than in other parts of the country, and this cannot be explained by causes other than HIV. Such argumentation is flawed - simply because the region was selected for this study because of its higher mortality than in other regions of Uganda. There are many other possible causes for the increase in morbidity and mortality from infectious diseases in some areas of an African country. Irrespective of the actual causes of this increase, both hypotheses predict much higher mortality in the HIV-seropositive group than in the HIV- negative one, and the causes of this difference cannot be discriminated by either hypotheses. Nevertheless, mainstream AIDS-scientists try to present this difference as a proof of the official HIV-causes- AIDS hypothesis. For some reasons, they "forget" to pay attention to the mortality rate in the HIV-negative group, which is obviously lower than the usual rate in this region - in perfect agreement with the "HIV-is-only-a-marker" hypothesis and contradicting the "HIV-causes-AIDS" one.
5. Other explanations for correlation between HIV-seropositivity and AIDS
The central goal of this summary is to show that there is no proof that a positive test for HIV-antibodies is caused by any specific antibodies, and that non-specific immunoglobulins are highly likely to be the actual cause of HIV-seropositivity. Let us imagine if it were shown experimentally that HIV-seropositivity is caused by specific antibodies - that is, blood serum from HIV-seropositive individuals reacts (in significantly higher titers than serum from healthy controls) only with the "HIV-proteins", but not with any other antigens. Surely, this would refute the hypothesis described here. Would such refutation be a proof that HIV-seropositivity is actually caused by HIV?
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Even if it were proven rigorously that HIV exists as an exogenous transmissible agent (this has never been done [1-4]) and that HIV-seropositivity is caused by HIV-infection, it still cannot prove that HIV is the cause of AIDS. Correlation between HIV-infection and AIDS-defining diseases is equally explainable by the "HIV-is-a-marker" hypotheses, which hold that HIV is a benign passenger virus [17] and can easily infect only individuals with some deviations from normal health status, thus, being only a marker of such deviations. In this case, morbidity and mortality may be much higher in HIV-positive individuals than in their HIV-negative counterparts, but not because of HIV-infection. Critical reevaluation of the studies carried out in Africa (see section 5) demonstrates that the results support the "HIV-is-only-a-marker" hypotheses, and contradict the HIV-causes-AIDS one irrespective of the actual causes of HIV-seropositivity.
Conclusions
Specificity of antibodies cannot be established in serological studies with one antigen: it is necessary to prove that titers of the antigen-antibody reaction are significantly higher (than in healthy controls) only for this antigen, but not in respect to other antigens. Given that such multi- antigen serological studies have never been carried out, increase in non-specific affinity of immunoglobulins is the most likely cause of HIV-seropositivity. The problem is exacerbated by the use of "sandwich" tests (like ELISA and WB) - because they are abnormally sensitive to any increase in affinity of non-specific immunoglobulins. Besides the non-specific immunoglobulins, there are several other mechanisms which can lead to correlation between HIV-seropositivity and diseases, while not being compatible with the official "HIV-causes-AIDS" hypothesis. The main flaw of the mainstream AIDS-science is that no experimental or epidemiological studies have been designed and carried out to rule out such alternative explanations. There are no reasons to consider HIV-seropositivity as a reliable marker of a deadly disease. The main danger of HIV- seropositivity is of iatrogenic (caused by medicine) nature: such individuals are at high risk of being administered abnormally severe and prolonged "prophylactic" treatment (antibiotics, antiretrovirals). This iatrogenic effect is a direct consequence of the uncritical acceptance of the HIV-causes-AIDS theory.
Vladimir Koliadin Ph.D. is a Senior Research Scientist at The State Aerospace University in the Ukraine and a member of the American Mathematical Society.
Endnotes
Is a Positive Western Blot Proof of HIV Infection?
Papadopulos-Eleopulos et al, Bio/Technology 11, pp. 697-707, June 1993
http://www.virusmyth.com/aids/data/epwbtest.htm
[Abstract] It is currently accepted that a positive Western blot (WB) HIV antibody test is synonymous with HIVinfection and the attendant risk of developing and dying from AIDS. In this communication we present a critical evaluation of the presently available data on HIV isolation and antibody testing. The available evidence indicates that: (I) the antibody tests are not standardised; (II) the antibody tests are not reproducible; (III) the WB proteins (bands) which are considered to be coded by the HIV genome and to be specific to HIV may not be coded by the HIV genome and may in fact represent normal cellular proteins; (IV) even if the proteins are specific to HIV, because no gold standard has been used and may not even exist to determine specificity, a positive WB may represent nothing more than cross-reactivity with the many non-HIV antibodies present in AIDS patients and those at risk, and thus be unrelated to the presence of HIV. We conclude that the use of the HIV antibody tests as a diagnostic and epidemiological tool for HIV infection needs to be reappraised.
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In Russia, it was found occasionally that even relatively small dilution 3-8 times (when samples from 3-8 individuals are pooled together) often lead to negative results of ELISA, when one sample of the several ones was positive (if tested separately - not in the pooled). Technically this means that titers of [antigen-antibody] reaction was quite low - < 1:3 -1:8 - lower than standards of practical immunochemistry require.
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