Christopher J Noble,
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Alan F Miceli writes; "Surely it is the content of the paper that matters not its title.The quote from this study given by the Perth Group certainly supports the relevance of the study in this context.And what about the other four references? This sort of unreasoning and incomplete response is not worthy of a postdoctoral fellow. "
As I have stated before I encourage people reading this debate to read the references that the Perth Group provide. I would have thought the title would have provided a clue that the contents of this paper do not support the Perth Groups arguments.(1) If you had read the paper you would have realised this. Baba et al do not contradict the findings of Kestler et al (2) that nef deleted SIV is attenuated and does not cause AIDS in adult macaques. The Perth Group are using a rhetorical argument called a false dichotomy. They would have you believe that a virus is either totally pathogenic or totally non-pathogenic. Baba et al argue that the case with nef deleted SIV is somewhere in between. The pathogenicity of nef deleted SIV is significantly reduced, ie it is attenuated, it does not cause AIDS in adult macaques however there is some evidence that it may lead to disease progression in newborn macaques that are more susceptible to disease. There is nothing at all to contradict the argument that nef-deleted HIV is also attenuated and responsible for some cases of non-progression in humans. Is it possible that nef deleted HIV could cause disease in human neonates? Yes. Is it therefore dangerous to use nef deleted live HIV vaccines? Possibly.
The Perth Group also cite Huang et al (3) supposedly as evidence that nef deleted HIV is not attenuated. If you read the paper you will find that in one particular cohort of LTNPs there was no pattern of nef truncation or deletion. Hence nef deletion is not likely to be the only or even common cause of LTNP. Does this mean that nef deletion does not cause LTNP? No.
None of the papers that the Perth Group cited provided any evidence that nef deleted HIV is not extensively attenuated.
It is very important to read the papers that the Perth Group cite and not rely on their selective quoting.
The Perth Group have stated in this forum: 'For example, the specificity of PCR has never been determined using a proper gold standard. Even when a totally unsuitable gold standard such as the antibody test is used, the specificity of PCR varies from 0 to 100% leading researchers from different institutes in the USA to conclude "Our investigation produced two main findings. First, the false-positive and false-negative rates of PCR that we determined are too high to warrant a broader role for PCR in either routine screening or in the confirmation of diagnosis of HIV infection. This conclusion is true even for the results reported from more recent, high-quality studies that used commercially available, standardized PCR assays...We did not find evidence that the performance of PCR improved over time". (13)'
0 - 100% specificity sounds pretty bad as do the quotes that the Perth Group provide from the Owens et al paper. (4). What is interesting in this case is what the Perth Group do not tell you.
"In studies in which the design was rated as either 3 or 4, sensitivity ranged from 83% to 100%, and specificity ranged from 95% to 100%"
The studies used in this meta-analysis were ranked from 1 to 4, with 4 being the best, according various criteria in the study design.
The studies ranked 3 and 4 involved the investigator being blinded in both the PCR assay and reference tests. The studies ranked 3 and 4 also had a well defined PCR protocol and used reference tests both with diseased and non-diseased populations.
So we see that the best studies showed a very high correlation between PCR and antibody tests. If the tests are totally non-specific as the Perth Group claims then the opposite would be true. The better controlled studies would show no correlation between PCR and antibody tests.
How does the Perth Group explain the correlation between PCR and antibody tests? They ignore it.
Why didn't the Perth Group quote this part of the paper? Because it contradicts their arguments.
If the Perth Group writes an article with hundreds of references at the end it does not make it a scientific article. It is necessary that the cited references actually support the arguments stated in the text. I have already provided a number of examples where the references given by the Perth Group do not support their arguments. Peer review would address some of these points but the Perth Group circumvent peer review by publishing on the internet.
This gets back to the original subject of this debate, the politics of AIDS. The so-called controversies in South Africa are not kept alive by science but rather through politics and rhetoric.
(1) Baba, T W, Jeong, Y S, Pennick, D, Bronson, R, Greene, M. F, Ruprecht, R. M. Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. (1995) Science 267:1820-1825
(2) Kestler HW, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. (1991) Cell 65:651-662
(3) Huang, Y, Zhang, L, Ho, DD. (1995) J. Virol. 69: 93-100.
(4) Owens DK, Holodniy M, Garber AM, Scott J, Sonnad S, Moses L, Kinosian B, Schwartz JS. Polymerase chain reaction for the diagnosis of HIV infection in adults. A meta-analysis with recommendations for clinical practice and study design. (1996) Annals of Internal Medicine 124:803-15.
Competing interests: None declared