Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso
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More on the specificity of PCR and its correlation with the antibody test
In his rapid response: "Re: Is there proof of a correlation between the "HIV" antibody and PCR tests and what may underlie such a correlation?", 15th December, Christopher Noble wrote: "The Perth Group are once again attempting to deceive the readers of BMJ. They write: "Most importantly, although these five studies may have been blind they may not have had controls as Owens et al point out. Thus it is not possible to state how many if any of the studies in the meta-analysis were indeed blind controlled studies." The meta-study clearly states that all studies that were awarded a rating of 4 or 3 used both negative and positive controls (see table 1). These same studies were also blinded, thus these 11 were blind controlled studies."
Firstly, of the 11 studies 6 were said to be blind but did not satisfy 4/8 of the other criteria. For example the "diseased" and "control" population may have received different reference tests. Which means any data from these studies has to be questioned even if the studies were blind-controlled.
Secondly, in the Owens et al study the criteria for being blind were: "the PCR assay and the reference test were done with the investigator blinded to all other tests and clinical information". It is not clear if there was "adequacy of blinding during the interpretation of test results" in all these studies.
Thirdly, it is not sufficient merely to have controls — the controls should be meticulously chosen to deal with the scientific problem at hand. That is, the controls need to be proper. The controls should not be a "non-diseased" population and even less blood "donors" as is the case in the Owens et al analysis. The control patients should consist of sick individuals diagnosed with diseases and laboratory abnormalities (such as low T4 cells counts, raised immunoglobulins and lowered levels of reduced thiols) resembling as closely as possible the abnormalities characteristic of AIDS patients. If improper controls such as “non-diseased” or healthy “donors” are used then virtually any test can be proven specific. This is because abnormal results are not to be expected in such individuals.
In fact it appears that Owens et al were aware that what they called controls were not proper controls. In their recommendations Owens et al wrote: "For example, the non-diseased population should include persons who are at risk for HIV infection and would be candidates for testing rather than healthy controls", which they used in their analysis.
Our question still stands: “Could Christopher Noble please tell us which of the 5 studies in the Owens et al analysis satisfied the criteria for a proper blind, controlled study or any other study apart from the one we have cited, that is, the Defer study"?
Christopher Noble wrote: "The Perth Group also attempt to argue that because the meta-study concluded that "Clearly, the performance of PCR is not adequate to justify its use as a clinical screening test" that this means that "neither the specificity of the PCR nor its correlation with the antibody tests has been proven". This is a non-sequitur. The study clearly shows that PCR results and antibody results are correlated. At least for the present, the specificity and sensitivity of PCR tests are lower than those for antibody tests. It is for this reason that antibody tests are recommended, where possible, rather than PCR for the diagnosis of HIV infection. It is quite simple to see that when there are two tests the one with the highest sensitivity and specificity should be used. It does not mean that the second is completely non-specific as the Perth Group would have us believe."
How does Christopher Noble know that "the specificity and sensitivity of PCR tests are lower than those for antibody tests"?
Let us return to some basic scientific principles:
In our Rapid Response "Is there proof of a correlation between the "HIV" antibody and PCR tests and what may underlie such a correlation", 11th December, we wrote: "To claim that the PCR is specific for "HIV" infection it is absolutely necessary to: (a) have proof that the primers originate from HIV particles. We have repeatedly asked Christopher Noble and Brian Foley to provide references which show this is the case but so far they have failed to do so; (b) show by the use of a gold standard that the PCR amplifies only HIV sequences and nothing else. As Owen et al pointed out, no such gold standard exists, a view shared by one eminent "HIV"/AIDS expert, William Blattner."
How then does Christopher Noble know what is the specificity of PCR? Is it 0%, 100% or a number anywhere between?
In our Rapid Response: "A plea to Christopher Noble", 8th August 2003, we ask for "A few references which prove that the “HIV” antibody tests are specific. To claim proof for specificity there must be at least one study and a few confirmatory studies where the antibody antigen reaction (assuming that the antigens are HIV) is compared with the presence or absence of “HIV”, that is, with “HIV” isolation/purification. This study must include a statistically significant number of both patients who have AIDS as well as patients who do not have AIDS but are sick. In addition the tests must be done blind."
Neither Christopher Noble nor anyone else has given us such references. In addition: (a) according to William Blattner  no gold standard for the HIV antibodies exists; (b) even if such a gold standard existed, the fact that the criteria for a positive test vary from continent to continent, country to country and even laboratory to laboratory means that the specificity of the antibody tests cannot be determined.
How then does Christopher Noble know what is the specificity of the antibody tests? Is it 100%, 50% or even zero? How does he know which test is more specific? Is it the PCR or the antibody test? How does he exclude the possibility that both tests are totally non-specific?
Christopher Noble wrote: "So, I return to my original question. How can the theories of the Perth Group account for the correlation between the results of PCR and antibody tests for HIV infection? The observation of this correlation does not depend on the assumption that HIV exists."
Firstly, before one tries to explain a correlation, first it must be proven that the correlation exists. Let us repeat, the only way to prove a correlation between the antibody test and the PCR is to perform blind controlled studies using proper controls and which also satisfy at least all the other criteria cited by Owens et al. We have asked Christopher Noble to give us a few such studies, including any of the 5 studies in the Owens et al analysis rated 4 which would satisfy all this criteria. So far he has given none.
Christopher Noble wrote: "I am interested in hearing how their oxidative stress theory predicts this observation. I am still waiting for the Perth Group to respond without evasion or bold lies."
Someone like Christopher Noble who carefully analyses our published work would have no problem realising why, in our view, oxidation in the absence of HIV leads to a correlation between the antibody and PCR tests. Briefly,
(1) The oxidising agents to which the AIDS patients and those at risk are exposed would cause the appearances of AIDS , that is, infectious and non-infectious diseases and thus high levels of antibodies including MCA, that is hypergammaglobulinemia and thus a positive "HIV" antibody test;
(2) The oxidising agents, to paraphrase Barbara McClintock  cause a "….."shock" that forces the genome to restructure itself in order to overcome a threat to its survival", thus leading to the appearance of novel non-viral RNAs, which may be detected with PCR. (Let us not forget that to date nobody, not even Gallo, has proven the existence of the "whole HIV genome" in the fresh lymphocytes in even one AIDS patient).
Since oxidising agents induce both hypergammaglobulinemia and novel RNAs an apparent correlation between antibody and PCR tests may be detected in the total absence of “HIV”.
1. Blattner WA. Retroviruses. In: Evans AS, editor. Viral infections of humans. 3rd ed. New York: Plenum Medical Book Company, 1989:545-592.
2. Papadopulos-Eleopulos E. Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? Med Hypotheses 1988;25:151- 162. www.virusmyth.net/aids/data/
3. McClintock B. The significance of responses of the genome to challenge. Science 1984;226:792-801.
Competing interests: None declared