"
And going to the university and the University of Florence in particular, it came out that Professor Ruggiero – that’s myself – was in absolute terms the Best Professor in the Entire University... and not only in biology and medicine but overall, concerning all the professors of the entire university" - Dr Marco Ruggiero, Professor of Molecular Biology at the University of Florence.

"Derrida's method consisted in demonstrating the forms and varieties of this originary complexity, and their multiple consequences in many fields. He achieved this by conducting thorough, careful, sensitive, and yet transformational readings of philosophical and literary texts, to determine what aspects of those texts run counter to their apparent systematicity (structural unity) or intended sense (authorial genesis)."
- Wikipedia: Jaques Derrida (and also copy-pasted to 2,520 other websites)

"I have long ago given up looking at anything from Snout... He has no credentials at all to discuss the things he talks about, yet feels free to denigrate a long-established, peer-reviewed Italian journal, and highly competent, even distinguished scientists and scholars. If anyone prefers to take his opinion rather than mine, I think that shows rather poor judgement in view of the curriculum vitae posted on my website and the anonymity and missing C.V. of Snout…"

- Henry H. Bauer. Professor Emeritus of Chemistry, Science Studies and Dean Emeritus of Arts and Sciences, Virginia Polytechnic Institute and State University.

Monday, August 3, 2009

Your comment is awaiting moderation... (part one)


The following bundle of notes was delivered to Snout's kennel a few days ago, apparently from Fulano de Tal (who from this photograph seems to bear an uncanny resemblance to Antonio Banderas).
SeƱor de Tal has suggested they may be of interest to Reckless Endangerment readers, and so we're publishing them in two installments over this and the next RE post. - S.




Fulano de Tal’s comments on “The “science” of AIDS” by Henry Bauer (HIV/AIDS Skepticism, Tuesday 28th July 2009)

Fulano’s generous assistance to the denialist cause has been spurned! He says it is because I promised to reveal my true identity, but that I reneged. But this is a lie! I sent Dr. Bauer a genuine Fulano de Tal birth certificate. But this was not good enough. He is an HIV/AIDS denialist and a Fulano birther on top of it!

I have come to the startling conclusion that he does not post my contributions to denialist literature because they are critical of his “work”! So I am forced to air my contributions here. This is very long, but that is only an indication of the rich “growth medium” for correction and criticism provided by just one single post of Dr. Bauer.

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Fulano de Tal said
Your comment is awaiting moderation.
Wednesday, 29 July 2009 at 12:01 am


Dear Dr. Bauer, I am wondering if you could clarify your interpretation of the quote from the NIH treatment guidelines:

“In the era of combination antiretroviral therapy, several large observational studies have indicated that the risk of several non-AIDS-defining conditions, including cardiovascular diseases, liver-related events, renal disease, and certain non-AIDS malignancies [14-19] is greater than the risk for AIDS in persons with CD4 T-cell counts >200 cells/mm3; the risk for these events increases progressively as the CD4 T-cell count decreases from 350 to 200 cells/mm3.”

As I read it, this passage is making two points: 1) antiretroviral therapy has drastically reduced the morbidity mortality in HIV+ persons from opportunistic infections, so that they are now more likely to get non-AIDS diseases; and 2) the risk of these diseases increases with the degree to which the immune system is compromised.

The very next paragraph in the treatment guidelines cites the SMART study results, showing that the risk of dying from non-AIDS conditions (hepatic failure, renal failure, cardiovascular disease, non-AIDS malignancy) was greater in those that received intermittent HAART compared to those who received it continuously, and was greater in those who delayed initiation of treatment until their CD4 T-cell count dropped below 250, compared to those who initiated immediately. It looks like the more HAART people get, the less their risk from dying of these non-AIDS conditions. The reason for the increased risk of some of these conditions in HIV patients is a hot area of research, but the data provide no reason to suspect that HAART is the culprit.
Why do you use this as a basis for claiming that HAART kills? Would you say that antibiotics, vaccines, and modern sanitation kill because they have allowed millions of people to live long enough to be cut down by heart disease and cancer?

Yours respectfully,Fulano de Tal

Reply

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Fulano de Tal said
Your comment is awaiting moderation.
Wednesday, 29 July 2009 at 1:49 pm

Querido Henry, and MacDonald:

I’d like to help you understand the nevirapine study. You are reading the results as self-contradictory because you are misinterpreting this statement:

“Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.”

As a simple matter of logic, this statement does not imply that antiretroviral therapy with nevirapine is not relatively well tolerated in patients with low CD4 counts. I am familiar with this problem since I run into it with my wife. If I say “I like the way you’re wearing your hair,” she sometimes makes the same fallacy you are making and replies “So what’s wrong with the way I had it yesterday?”

But looking at the context, it is clear that the authors are adding this group of patients to those in whom nevirapine has already been shown to be safe enough. They point out that there has been a recommendation not to use the drug in patients with high CD4 counts. That is why they make their statement, suggesting that that recommendation be revised in the case of antiretroviral-experienced patients with high CD4 and undetectable viral load.

In their introduction, the authors provide the rationale:

“Among HIV-positive patients, the risk of hypersensitivity reactions is highest in patients with higher CD4 cell counts, with a lower CD4 threshold observed in women. Asians may also be at an increased risk [12]. This has led to the recommendation not to use nevirapine in HIV-1-infected patients starting nevirapine at higher CD4 cell counts (>400/ml in men, >250/ml in women) [13], unless the benefits clearly outweigh the risks. This recommendation is based on data from clinical trials in treatment-naive HIV-1-infected patients. It is, however, unclear whether the risk of potentially fatal toxicities is increased similarly in other patient groups starting nevirapine-based cART (NVPc), for instance treatment-experienced patients starting NVPc for the first time with high CD4 cell counts.”

This is why they conclude, based on their new data, that the risk of reactions is sufficiently low in this one class of high CD4 patients, adding this group to all low-CD4 patients in whom the safety of nevirapine is already established. No contradiction here.


I hope this helps to clear things up.

Abrazos,
Fulano de Tal

Reply
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Fulano de Tal said
Your comment is awaiting moderation.
Wednesday, 29 July 2009 at 9:35 pm

Dear Dr. Bauer,

I am starting to feel like you are deleting my posts because you don’t like criticism. I know that is not a nice thing to think, or say, but it’s the natural conclusion to draw. I have never argued that HIV is the cause of AIDS, or that it is not. I have only pointed out mistakes and problems in things you have posted. When I first did this, you were grateful to have some peer review. Maybe some of my criticisms were harsh, but they were never wrong. It was you and Darin Brown who said that I was trying to prove HIV/AIDS and disprove denialism, but you can look closely at everything I’ve written and you will see that I only criticized specific claims and analyses on your blog.I know you don’t delete all my posts because you don’t believe I am really Fulano de Tal, because you allow posts by “Cytotalker,” “SkepticThough,” and “Dave.” I can only believe it is because I point out problems with your work, which the other commentators almost never do. This is unfortunate and of course contrary to the open discussion and spirit of inquiry you wanted to foster on your site. I am sorry you won’t take advantage of the sharp scrutiny of someone who knows much more about research methods and biostatistics than you.

Abrazos,Fulano de Tal

By the way, why did you write that KS is “a non-HIV/AIDS condition”? Kaposi’s sarcoma is caused by KSHV. But the virus is generally latent except in immune-compromised persons. “AIDS-related Kaposi’s sarcoma” is a medical term for KS when found in patients who are immunocompromised due to HIV. So the problem kind of is HIV, since the likelihood of developing KS in KSHV infected people without HIV is exceedingly low.

Now for the paper in question: It looks at only HIV+ patients with KS. The paper cites five existing studies that show a decline in the incidence of KS in HIV patients with access to HAART. Now they want to show what happens in patients that do get KS and are treated with HAART. These are not healthy people. Pre-HAART-era prognosis for AIDS-related KS is about 10-20 months median survival, i.e. 50% are dead in 10-20 months. This study shows that the overall survival of AIDS-related KS patients treated with HAART after 5 years was 90% — that’s 10% dead in 60 months.

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Note: Installment number two should be published in a few days.
-S.




13 comments:

Tokoloshe said...

Senor de Tal,

You are making a terrible mistake in thinking that the mighty MacDonald could conceivably be Fulano's Vain Wife fallacy.Did yu not read the last part of his post where he states:

Are we to understand that if the patient has a high CD4 count and ARV experience, the side effects are not as bad as if the patient has a high CD4 count and no ARV experience?

In this case it just means that the drug should primarily be given to those who have proven that they can endure similar drugs.

And that is indeed the conclusion, isn't it? The risk is high in treatment naive persons with high CD counts, but all other things being equal,it is acceptably low in treatment experienced persons.

But since you're already at it, perhaps you could make some more sense of this study for us:

HIV-1- seronegative adults using nevirapine for postexposure prophylaxis appear at particularly high risk of lifethreatening hepatotoxicity [11]. Among HIV-positive patients, the risk of hypersensitivity reactions is highest in patients with higher CD4cell counts”.

Are we to conclude that HIV sero-positivity and low CD4 cell counts protect against
hepatotoxicity?

Your thoughts on this curious matter are greatly appreciated.

Besos

Toko Loco

Anonymous said...

Querido Loko,
Thank you for reading so carefully! MacDonald is right on the point that you bring up. In patients with high CD4, extra caution should be used in giving nevirapine. So it's still prudent not to recommend it for the ARV-naive.
But this is not why MacDonald said the study is self-contradictory. He said that because the authors say that nevirapine can be tolerated in this group of high-CD4 patients, when previous research has found more reactions with high-CD4. But it is not contradictory, because earlier studies did not include treatment-experienced patients. Therefore the authors revise the recommendation in light of their new findings.

So I will concede that maybe MacDonald did not commit the same fallacy as Dr. Bauer, but he was guilty of forgetting to remove his blahblah glasses.

The bigger point is the lesson that is inscribed on the de Tal coat of arms: "Do not ridicule a piece of research without understanding it first. If you do, you might end up looking ridiculous yourself and revealing your biases."

As to your second question:
Are we to conclude that HIV sero-positivity and low CD4 cell counts protect against
hepatotoxicity?

That's what the research suggests, so it's good to err on the side of caution. Don't give nevirapine regimes as post-exposure prophylaxis or to high CD4 patients!

Abrazos,
Fulano de Tal

Tokoloshe said...

But my dearest Senor de Tal,

I don't think the mighty MacDonald was ridiculing the paper,just genuinely trying to understand what was meant. I'm sure he appreciates your clarification and superior skills in getting inside the mind of ARV and HIV enthusiasts.

But, my dissident friend, how could immune-deficieny and acknowledged infection with one of the most deadly microbes the world has ever seen protect against drug side-effects?

You do realise that here we might have stumbled on a clue to why Duesberg's dose-related AIDS theory doesn't apply so straighforwardly these days?

Anonymous said...

Toko, ffs, what do you think mediates a hypersensitivity reaction?

Rev. Howard Furst said...

HIV begets anergy. HIV infection often depresses tuberculin reactions (etc.), and the same depression of immune system reactivity underlies the reduced incidence of hypersensitivity reactions to drugs among HIV infected people. Even a scientifically illiterate man of the cloth such as my esteemed self can figure that out.

Tokoloshe said...

Right, right, anergy. I bet that is why people come down with leprosy and TB when their immune systems reconstitute, except in this case high CD4 is actually ok, Senor de Tal just told us that, but detectable viremia is not ok.

Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia”

Is this because HIV begets less anergy the more active it is?

Rev. Howard Furst said...

I can see by your rhetorical skills that you would make a fine Theologian; in fact I recommend it since in that field no one can successfully call BS on your specious reasoning, nor contradict you with evidence-based understanding. We have an opening in the Furst National Church for a trainee Inquisitor. Would you like to give it a try? Our salaries and benefits are quite competitive, and our tithe-sharing system was devised by Father Ponzi in the Rome office, if you know what I mean.

Rev. Howard Furst said...

But just to humour you, I will proffer the suggestion that some symptoms and features of leprosy and TB are due to reactions of the immune system and not solely to direct actions of the offending pathogens as you slyly imply. If one doesn't naively mix "diseases of action" with "diseases of reaction", many of these fascinating of yours conundrums can be resolved without recourse to the advice of clergy, and also without public embarrassment.

Tokoloshe said...

Dear Rev.

I fully accept your authority - how cold I not in view of your title?- also when it comes to the mysterious ways of the immune system.

I was simply pointing out that in this paradoxical case absence of immune-suppressing viremia was a provision. Suppression of viremia and increasing CD4 counts, is that not the very basis for Immune Reconstitution Syndrome?

You said, and I agree:

depression of immune system reactivity underlies the reduced incidence of hypersensitivity reactions

But the authors say:

"Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia"

So I was merely wondering, why the emphasis on no viremia. I must impress on you that it is a perfectly innocent question. I have not read the paper and the whole thing is probably explained in it. Note also the second provision that the person must have had previous ARV experience. An altogether curious set of preconditions.

Anonymous said...

Querido Tokoloko:
Fulano has read the study. It looks like viremia does have a big effect on hypersensitivity reactions. This is consistent with some other studies, and might be due to immune hyperactivation in these patients.

Greater tolerance among treatment-experienced patients is a well known result. It should not come as a surprise to anyone that experience produces tolerance:
http://www.aegis.com/pubs/aidswkly/2002/AW020702.html

None of this is very curious.

I hope you find this helpful, Pedrito (if I may call you that).

Abrazos,
Fulano de Tal

Rev. Howard Furst said...

Tokoloshe, I had one of the Altargrrlz [TM] from the Church try to track down the paper, for which the journal wanted to charge $35 of my hard-earned tithe appropriations. A contemporaneous free paper by the same authors on the same subject (CV padding?) included the nonilluminating passage below. They note the phenomenon of lower incidence of hypersensitivity reactions to nevirapine in patients with a low viral load, but don't fully understand why, other than proffering mealy-mouthed notions of immune hyperstimulation. That failure alone is sufficient to undermine the entire "HIV causes AIDS" hypothesis.


"We previously reported that patients starting NVP therapy with an undetectable viral load appeared to have a low incidence of HSR [Edit: HSR = hypersensitivity reaction]. The current analysis corroborates these findings. A possible explanation is that, when HIV replication is controlled, the lower antigenic HIV load results in less immune hyperstimulation, which, in turn, might reduce the tendency of the immune system to overreact to the institution of NVP treatment. This hypothesis, however, does not explain why HIV‐seronegative adults, who would not be expected to have hyperstimulated immune systems, are prone to developing life‐threatening HSRs while receiving NVP therapy."

As a gesture of reconciliation, I hereby offer you Salvation for a discounted tithe of only 8% of your gross income. Guaranteed nonstop and unchallenged entry to Heaven post-mortem or your money back.

Effervescently yours,
Rev. Howard Furst

Tokoloshe said...

Dear Rev.& Snout,
I am always open for money back guarantees, but it is probably wiser to issue those in the realm of religion than science

Thank you very much for your input. On rare occasions,
scientific, or religious if you will, curiosity becomes a force stronger than partisanship.

One of our tasks, gentlemen, is to find seeming contradictions in order to advance our understanding through confusion, instead of remaining forever suspended in a leap of faith.

We have now in both of setop threads glimpsed complex patterns of cause and effect that have not yet found a simple explanation, which is humbling. Let us pray that the Watchtower will never be unmanned.

Anonymous said...

AIDS. 2005 Jan 3;19(1):97-9.

Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts.

Martin AM, Nolan D, James I, Cameron P, Keller J, Moore C, Phillips E, Christiansen FT, Mallal S.
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia.

Genetic (human leukocyte antigen), disease-related and demographic risk factors for nevirapine reactions were examined in a nevirapine-exposed cohort. Cases involving combinations of hepatitis, fever or rash were associated with an interaction between HLA-DRB1*0101 and the percentage of CD4, whereas no associations were detected for isolated rash. These data suggest that HLA-DRB1*0101 and the CD4 status may determine susceptibility to nevirapine hypersensitivity, consistent with a CD4 T-cell-dependent immune response to nevirapine-specific antigens.