Dean's World

(By the way, while I said I'd probably try to stay out of the fray here, if I can't resist and wind up commenting, and you see me breaking my own rules, call me on it. I'll have to arrange a suitable punishment for myself if I do.)

It would seem to me, honestly, that if we are going to get into arguments over the accuracy of tests, we wind up back at square one: if the tests are acknowledged to be primitive and unreliable, what are we supposed to base our epidemiological data on?

They began testing the blood supply around 1984 or 1985 if I recall correctly, and that's considered reliable enough and safe enough to allow transfusions to proceed. Can we stick to that as our yardstick? Testing of the US blood supply? Because from everything I can see that's what these figures are founded up on: what's found in the general blood supply, military recruits, and what hospital labs and doctors offices report finding en masse.

As for Africa: I've been trying to restrict to the US solely for the purposes of keeping the discussion simple, and hoped to address Africa at another time. I won't say no, but... I really think waiting a bit longer would be prudent.

Dean,
Blood donors and military recruits showed HIV rates which suggest far less than 1 million HIV carriers. It was assumed that this is because high-risk groups are left out (i.e. not too many homosexuals among the recruits). There is no data that gives 1 million HIV carriers without certain debatable assumptions. Hence the enormous range mentioned in the 1987 report:
"The range of estimated values is large, from 276,000 to 1.75 million persons infected, reflecting both uncertainty in the progression rate for AIDS and the varied assumptions about the shape of the underlying infection curve. With use of only the best estimate of the disease progression rate from the San Francisco prospective study, the range of estimates is smaller, from 420,000 to 1.65 million."

Dean -
Thank you for sticking with this. I've been reading - but not contributing - because I haven't had anything worthwhile to add. And because there's been too much of it for me to keep up with.

Don't let some snarkiness in some comments get you down. You know that people with strong opinions are more likely express them. Even moreso when their opinion opposes yours. You're triggering a lot of thought, here - and probably most of those thoughts don't turn into published comments.

Keep it up.

(...back to lurking, now...)

I was gonna go through and check the sources, and in doing so I found this statement from http://www.cdc.gov/mmwr/preview/mmwrhtml/00001894.htm:

"On the basis of these back-calculation analyses, CDC now estimates that approximately 750,000 persons in the United States were infected with HIV at the beginning of 1986 (Table 1). Estimates of current HIV prevalence based on these analyses range from 650,000 to 1.4 million. The median of these estimates is greater than 900,000, and only one estimate is less than 850,000. The wide variation among the estimates for recent years reflects the sensitivity of the back-calculation approach to more recent surveillance data reports and to varying estimates of the distribution of incubation times.

The group agreed that back-calculation provides a basis for estimating past HIV-infection prevalence and future AIDS incidence. However, the accuracy of this method depends on the validity of the necessary assumptions and adjustments made, especially those concerning the completeness of AIDS case reporting and the estimated distribution of incubation periods. Current estimates derived from empirical data."

First, it seems they wanted to change their 1986 estimates...lower (although the next paragraph is vague as to whether that was accepted). But the other important point is that they are making these projections based on AIDS and HIV data...not just HIV data. It's a back calculation that assumes HIV causes AIDS. No? Am I missing something?

At any rate, I don't like the idea of picking the high end of Curran's numbers and the low end of the next set of numbers to fit the graph.

Enjoy the discussion!

Dean, I just have to add this. Please. I hope I don't get kicked out, but if HIV testing HUGE relative samples of the population in the US gives these problems Maor has called our attention, then can you imagine estimating Africa?

"there three kinds of lies: lies, damn lies, and statistics"

Of course, a statistician will say that Twain was referring to inappropriate use of statistics to make an incorrect point. IMHO, that's what Bialy did.

Maor:

You are quite right: "HIV was linked to AIDS by the near 100% HIV prevalence in AIDS patients, the correlation between HIV and death of individuals, and by the correlation between HIV behavior and AIDS symptoms".

I find interesting, though, that after 20 years "HIV behavior" continues to correlate very well with AIDS, whereas HIV test-based estimations do not, we all agree now, correlate very well with anything. AIDS continues mostly restricted to risk groups and estimations into the general population..., well, see above.

However, I would have expected, with the benefit of hindsight, that those 20 years and zillion HIV tests would have added confirmation to the original underlying assumptions, not muddled them.

And I also agree with you that a statistician would say just that too. It was only a jocular comment. But the fact remains that the CDC used those same shaky stats to terrify everyone, with or without "HIV behavior", by placing almost exclusive emphasis on HIV and excluding the behavior bit (if you have to keep shooting up, use clean needles, etc). Which leads us to some of the very questions Dean put forth when starting this new thread.

Samba

jfr,

I think maor knows that correlation doesn't equal caustion...lol, but as has been stated before, there are other reasons for thinking HIV causes AIDS...not just the fact that "HIV and AIDS have been linked in time, place, and population group." ( I believe that's how the phrase goes...lol)

Jeremy, I agree. The guestimates could also be used in a descending trend or in just about any trend. So they don't tell us anything, which is a point that Maor has made and which I agree with. Duesberg only quoted the averages as used by the CDC.

Of course that it is pointless "Trying to disprove an assumption based on numbers that rely on that assumption". I agree with you and I am not trying to do that. But if zillions of HIV tests still don't tell you anything, then I think we are back in 1987 and questioning HIV as a pathogen on virological grounds, as Duesberg did in the Cancer Research review on retroviruses.

The epidemiology may find correlations and, as the statistical science that it is, it can expect to confirm/change many things as samples get bigger and bigger. And, in my opinion, it has. It has confirmed that "HIV behavior" still correlates very well with AIDS and that the "explosion"into the general population has not occured (not in the US and Europe, at least; but I don't want to get goin' on Africa ..., not yet anyway).

I hope you don't get the idea I am trying to convince you of anything. You express your doubts about some ideas, and I do the same. Civilly, amicably, and we leave it for the rest of the readers to benefit from our exchange. That is all.

Samba

Jeremy, I wonder if you really want the debate to stay "sane", as you put it.

Africa, as a rule, may suck politically according to you. But Western reporting about how much exactly Africa sucks, and why, and where, and how, sucks far more than Africa itself, and is not to be trusted either.

Try to be less offensive, we are talking science, not politics, and the internet is global, and Dean did not specify that you have to be from the developed world to participate.

I wonder how many people would jump to my throat if I said that, as a rule, America sucks. And if that would not be enough for Dean to, justifiably, cut me off the thread.

Samba

Samba, I think you make a really good point, at least tangentially:
Supporters of the HIV = AIDS theory are saying that the theory was established in good faith with acceptable information established to within acceptable tolerances, and there just isn't enough certainty in the counter-evidence to do anything.
Opponents of the HIV = AIDS theory are using logical chains of supposition to demonstrate that HIV = AIDS.
Now, I'm pretty much in the "Opponent" camp spearheaded by Dean (although I was there months before he even started).
It seems to me, much like the Monty Haul Door Puzzle Dean brought up again to bolster his point, if you can't see/understand the logic, you deny it is even there.
It's like a logic puzzle. On the surface of it, 5 simple statements could not give you enough information to determine what nationality lives in what color house, drinks what beverage, smokes what tobacco and has what pet...but if you rigorously follow all the implications, the answer is clear. That's what Bialy, Duesberg, and Dean are doing.

What bothers me the most about all the arguments is that some of the supporters of the HIV = AIDS theory consider their own impressive-but-not-exactly-relevant-credentials and native layman intelligence to be good enough to refuse to credit Dean's own native intelligence to make these logical conclusions. And further, are using those same credentials/intelligence levels to refuse to consider and evaluate the chain of conclusions.

It's frustrating.

Samba,
Ypu say:
"I find interesting, though, that after 20 years "HIV behavior" continues to correlate very well with AIDS, whereas HIV test-based estimations do not, we all agree now, correlate very well with anything."

1)By "HIV behavior", I meant the physiological behavior of the virus in the body (i.e. it infects the same cell type which is depleted in AIDS)

2)HIV estimates DO correlate with AIDS cases (A bit over half of HIV carriers who ever lived have already developed AIDS). Of course, HIV estimates are partially based on AIDS cases, so this would be expected.
Only the TRENDS in HIV estimates are too fuzzy to be of any use (The early estimates at least. More recent estimates might be useful for predicting the future, but the future is in the future, eh?).

Nathan writes: "What bothers me the most about all the arguments is that some of the supporters of the HIV = AIDS theory consider their own impressive-but-not-exactly-relevant-credentials and native layman intelligence to be good enough to refuse to credit Dean's own native intelligence to make these logical conclusions. And further, are using those same credentials/intelligence levels to refuse to consider and evaluate the chain of conclusions.

It's frustrating."

Speaking as an AIDS Apologist, I think I can say the frustration is mutual. My perspective is that all data is not equal and cannot be given equal weight. I expect that's your perspective or Dean's perspective as well. But we disagree on which data should be given the most weight.

For example - in reconciling these two graphs of hiv versus aids incidence/prevalence. If I ignore the clinical latency of the virus (for which there is all kinds of evidence based on following what happens in hiv infected individuals), if I ignore the fact that public awareness has reduced high risk behaviours(based on questionaires given to high risk individuals), if I ignore the large measure of uncertainty that was necessarily a part of the early estimates (because the definition of AIDS was changing, the estimates of latency were changing, the proportion of at risk people being tested was changing), if I ignore the studies that say that treatments have reduced mortality and more recent treatments (i.e. HAART) may also be reducing transmission - if I ignore all these things then I agree completely that I cannot reconcile those two graphs. However, since all those things are part and parcel of the hiv/aids hypothesis, I can't ignore them and so I don't see the graphs as requiring explanation.

Daf9,
You make an excellent point about the weight each side correspondingly gives differing evidence.
However, your very first example is the introduction of a strawman, and an extremely inaccurate one at that:
You don't have to "ignore latency" to see Dean's graphs as indicating the idea that HIV does not cause AIDS. In fact, to preserve the theory that "HIV Causes AIDS", you have to use the concept of latency in ways in was never meant to be used, almost as a magic wand to wave away any data irregularities that would undermine the "HIV Causes AIDS" theory.
The second is another strawman: as soon as AIDS-treatment drugs hit the market, 'safe sex' went out the window for a significant population of homosexuals, if not heterosexuals. I don't think 'safe needle use' ever really caught on. And there was a report just about a year ago about a significant increase in syphillis infections among homosexual males...but no corresponding significant rise in HIV/AIDS sufferers. That cannot compute...
And the "inaccuracy of early data" isn't a winning argument for your side, either. It's already been refuted. Heck, if your side was right that HIV Causes AIDS and that AZT saves lives, then the death rate of high-risk groups mustgive us extremely accurate estimates of the early rate of HIV prevalence. If it doesn't, then that already invalidates the HIV=AIDS theory.

However, despite what I respectfully consider to be insufficiently compelling examples, your point remains exactly correct: a difference of focus is probably causing both sides to talk past each other, much like the blind men and the elephant.

Hank Barnes writes: "...Duesberg makes another point about the drugs used to treat AIDS, namely this one little bugger called AZT.....7. However, AZT kills all types of white blood cells -- the whole lot. The whole police force.

8. It does this by terminating the DNA of any and all quick-dividing cells. It cannot differentiate between the DNA of a virus and the DNA of a cell. In fact, the latter has millions of more nucleotides than the former. It is a much easier target.

Anyone wanna tackle this on the merits?"

Okay Hank. First to clear up a misconception of how AZT works. Within the cell there are pools of deoxyribonucleotides that are required to replicate DNA. For the cell's DNA the replication process requires an enzyme called DNA polymerase. When DNA polymerase incorporates AZT it will stop the replication process at that point. The enzyme required for viral replication is a different enzyme called reverse transcriptase. Reverse transcriptase is killed by lower concentrations of AZT than cellular DNA polymerase is.

The evidence that AZT really works this way in people is the observation that when hiv negative people are treated with antiretroviral medications including AZT (which is done for people who have been exposed to hiv containing blood to reduce the chance of infection) - in those people AZT causes no changes in CD4+ T cell counts.

In contrast when hiv positive people are treated with antiretroviral medications including AZT they show dramatic increases in CD4+ T cell counts and the increases in T cells generally correlate with the extent to which viral loads are reduced.

Dean, just a quick note. Your work has been absolutely outstanding.

Many people know I was diagnosed with a double wammy of immune disease and over the last year have gone through some horrible times with sickening side effects that took my mind up and down into depths I would sincerely never wish on anyone not even a so called enemy.

Since changing a lot of habits and believeing 100% in the medical establisment I went down hill. One drug, two, three six to ten with all side effects making me so sick and nausea that I started wiening myself off. If getting better meant ALL that hell, then I just wanted it to stop and the ups and downs as witnessed here in my posts showed that not enough is done in other areas of healing.

I am a walking, yes I say walking testimony. I moved from Chicago with the immune diseases of RA/Lupus and used a cane when I boarded that plane.

Question the medical field, never do what I di for so many years. I believed in alternative medicine but it wasn't until I was ready to give up that I found a fabulous chiro and natural healer. His partner works with sports medicine and athletcs come from all over.

Dr.Clayton and I will be putting out a newsletter and our first subject will be immune disease and will lean to RA but we will send you a copy and are probably looking at a way to incorporate your blog and other's that I know would benefit whole heartily. I am walking and sitting like when I was a young woman and even going to start ballet soon as it will enhance the stop the degenative bone disease.

Keep up this HIV, it is outstanding work and Dr. Clayton and me will be getting a hold of you in the future. My Body Flex has him thrilled for me and we are putting on a program in Febuary and I will be a Big Part of it.

Good for you hanging in there. Oh, I can not e-mail as someone we know took over somethings and it is not a family member but down the road you will know as my soon to be disconnect of this address and police going over all the things done during and still going on due to identity theft.

I'll be back and give the children a hug please. I am one busy woman trying erven harder now.

One more time...great work on the HIV and immune system!

From Debating AZT by Anthony Brink (Nov. 2000), linked by jfr in some other related thread.

[19] The negative Concorde trial results were entirely on par with those of an earlier French trial. In 1988 in the Lancet, Dournon et al had published a study of AZT, conducted at the Claude Bernard Hospital in France. It was wider and longer than the American Fischl trial that had preceded FDA approval, and at the end of it the researchers found AZT to be “disappointing.” They noted, “The bone marrow toxicity of AZT and the frequent need for other drugs with haematological toxicity meant that the scheduled AZT regimen could be maintained in only a few patients… by six months, these values [i.e. initial modulation of p24 antigen levels] had returned to their pretreatment levels and several opportunistic infections, malignancies and deaths occurred” - by nine months, about a third dead, another third very sick. But most significantly for the idea that AZT exerted an anti-HIV effect, “full-dose AZT for 2 months did not eliminate antigenemia in patients with pretreatment p24 levels of 200 U/ml or higher...[so] in AIDS and ARC patients, the rationale for adhering to highdose regimens of AZT, which in many instances heads to toxicity and interruption of treatment, seems questionable.” It bears emphasising that the dose was 200mg every four hours, the standard officially recommended dose, and the same as the dose given during the pre-approval Fischl trial in the US, yet the reported outcome was completely different.

Emphasis mine.

Samba

FDA DOCUMENTS SHOW FRAUD IN AZT TRIALS
By John Lauritsen
New York Native 30 March 1992

After an arduous three-month battle with the Food and Drug Administration (FDA), I have finally obtained documents which describe in detail many acts of fraud committed in the conduct of the Phase II AZT Trials. It was on the basis of the Phase II Trials that AZT was approved for marketing by the FDA in 1987.

Anyone who requests government documents under the Freedom of Information Act should be aware that he's in for a hard time. If the requested documents are completely innocuous, then the government will probably lose them through incompetence. If the documents are not innocuous, then dilatory tactics of every kind will be employed, on top of the usual incompetence. If the documents should eventually be found and released, they will be heavily censored.

On 12 December 1991 I filed my request with the FDA's Freedom of Information Staff, asking for various documents pertaining to the multi-center Phase II AZT trials conducted in 1986. My requests comprised the "Establishment Inspection Report" on the Boston center, written by FDA investigator Pat Spitzig, and two sets of minutes, written by Jackie Knight and Mary Gross. Three weeks after filing my request I got an acknowledgment. When I called the woman who sent it to me, she said that all three of my requests had been found, and I would get them soon. A few days later a form letter arrived from another woman, stating that none of my requests could be found, and my search had been completed. I began calling around until finally I got a Freedom of Information specialist within the FDA, Liz Barbakos, who went to bat for me. With her help, the people in Boston were able to re-find the Establishment Inspection Report by Pat Spitzig, and the people in Maryland (the FDA's headquarters) were able to re-find the Jackie Knight minutes, though not those by Mary Gross. Barbakos said I should receive them in a few days.

Weeks went by, and nothing arrived. I called Barbakos again, and she investigated. She called back to explain that the Jackie Knight minutes would be sent immediately, and that Barbara Recupero in Boston had had the Spitzig report on her desk for two weeks, and was waiting for her supervisor to give the OK before sending it. The next morning I got a conference call, with Liz Barbakos and Barbara Recupero on the other end. Barbakos said she wanted me to hear what Recupero had to say. Recupero said that she had no idea what document I was referring to. I then called Pat Spitzig, the author of the Boston Inspection Report, who called Liz Barbakos and told her exactly what the document was. This put an end to the stonewalling, and I received the 76-page report.

Almost every page was heavily censored. Obviously my difficulty in obtaining the document had nothing to do with problems in finding it - they knew where it was all the time. Rather, the difficulty derived from the FDA's unwillingness to let the document see the light of day, and the various censorship decisions that needed to be made once they realized that further stonewalling would be counterproductive.

The Mary Gross minutes are another story. On the first four times I called her, she was always "away from her desk", and my calls were not returned. On the fifth try I finally got her, and expressed my disbelief that she should be unable to find her own minutes of a very important meeting. The next day she called to say that something I said had triggered her memory, and she had found the minutes. She then faxed them to me, and I found that they consisted of a half page of nothing. For reasons I'll explain later in this article, I do not for one minute believe the minutes she sent me are genuine. Indeed, I regard the phony minutes I received as one more form of censorship, one more way the FDA has of circumventing the spirit and the letter of the Freedom of Information Act...


----------------------------------

Odd.

Samba

Maor, the Dournon study was LONGER then Fischl's.

From 100 more things about Dean:

"54) I am very nearly impossible to offend unless you question my intellectual integrity, or are willfully obtuse. If I accuse you of either, you can assume I'm very angry with you. In fact, if I call you "willfully obtuse" or "intellectually dishonest," you can safely assume I'm a lot angrier (or at least more irritated with you) than if I just call you an asshole or a fuckhead."

Samba

Samba,
The INITIAL Fischl study was shorter than the Dournon study.
Later studies by the Fischl group were longer than the Dournon study (for example, Ann Intern Med. 1990 May 15;112(10):727-37).


I'm a regular reader of Dean's World, so I know all about him ;)
Thanks for the warning, though.

Samba?
Perhaps you don't realise it, but I'm not defending AZT (on which I have no opinion). I am debating the idea that HIV carriers die from AIDS only because of AZT.

AZT not reducing mortality despite temporarily raising T-cell counts?
That supports the thesis that HIV, not AZT, reduces T-cell counts.
This is especially true of the statement:

“Triple therapy for HIV infected patients… do not have any unique effects on CD4 cell counts independent of reductions in plasma viral load”

AIDS therapy only raises T-cell counts by reducing HIV!
Tsk tsk!

From 100 more things about Dean:

55) I don't view ignorance as a bad thing, nor calling someone ignorant to be an insult. But I view willful, correctable ignorance on any matter of importance to be among the gravest of personal sins.

56) I view the pursuit of truth as the highest calling of the human mind. People who engage in circular or unprincipled arguments therefore tend to drive me into a rage. (It's probably that INTJ thing.)

70) I believe in facts. I believe you must always be prepared to surrender everything you believe in the face of an incontrovertible fact. I find people who can't do that to be either sad or infuriating, depending on my mood.

Samba

The spin maor was alluding to

From Debating AIDS

In 1991 in Laboratory Investigations, Lamperth et al reported Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model within three weeks of experimental exposure to “AZT at doses equivalent to the total daily dose used in acquired immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in tissue culture exhibited abnormal mitochondria characterized by proliferation…, enlarged size, abnormal cristae and electron-dense deposits in their matrix. The changes were partially reversible after AZT withdrawal. Rats treated with AZT developed weight loss, 100-fold elevation of creatine kinase, and increased serum lactate and glucose.” Corcuera-Pindado et al reported Histochemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle in the European Journal of Histochemistry in 1994: “We carried out an ultrastructural and histoenzymatic study in rat cardiac muscle. Groups of animals (3 rats per group) were given drinking water with or without AZT (1 or 2 mg AZT/ml). After 30, 60 and 120 days, the hearts were studied by light and electron microscopy... The ultrastructural study showed a disruption of cristae and an increased size of mitochondria in rats treated with AZT for 30- and 60-days.” Lewis et al reported that Zidovudine induces molecular, biochemical, and ultrastructural changes in rat skeletal muscle mitochondria in the Journal of Clinical Investigations in 1992: “Molecular changes in a rat model of AZT induced toxic myopathy in vivo helped define pathogenetic molecular, biochemical, and ultrastructural toxic events in skeletal muscle and supported clinical and in vitro findings. After 35 d of AZT treatment, selective changes in rat striated muscle were localized ultrastructurally to mitochondria, and included swelling, cristae disruption, and myelin figures. Decreased muscle mitochondrial (mt) DNA, mtRNA, and decreased mitochondrial polypeptide synthesis in vitro were found in parallel. Mitochondrial molecular changes occurred in absence of altered abundance of cytosolic glyceraldehyde-3- phosphate dehydrogenase, or sarcomeric mitochondrial creatine kinase mRNAs.”

[10] In his answer to my essay, Martin admits that AZT destroys bone marrow, but then hedges: HIV “may” be the real culprit. This is a tired old tale rehashed. Mercury and arsenic salts - doctors’ favourites for ages - poisoned the patient, whose death was then blamed on unbalanced humours or germs. That AZT destroys bone marrow is frankly declared by its manufacturer. So let’s not fudge. In 1987 in Annals of Internal Medicine, Gill et al reported Azidothymidine Associated with Bone Marrow Failure in the Acquired Immunodeficiency Syndrome (AIDS): “Four patients with [AIDS], and a history of Pneumocystis carinii pneumonia developed severe pancytopenia [marked decrease in all types of blood cells]…12 to 17 weeks after the initiation of azidothymidine therapy… Partial bone marrow recovery was documented within 4 to 5 weeks in three patients, but no marrow recovery has yet occurred in one patient during the more than 6 months since AZT treatment was discontinued.” In the same year in the New England Journal of Medicine Richman et al reported The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDSRelated Complex: “Anemia…developed in 24% of AZT recipients and 4% of placebo recipients (P<0.001). 21% of AZT recipients and 4% of placebo recipients required multiple red-cell transfusions (P<0.001). Neutropenia (<500 cells per cubic millimeter) occurred in 16% of AZT recipients, as compared with 2% of placebo recipients (P<0.001).” The next year, Walker et al followed up in Annals of Internal Medicine reporting Anemia and erythropoiesis in patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with zidovudine: “In the current study, transfusion-dependent anemia occurred in 6 of 15 patients with AIDS and Kaposi sarcoma who were receiving zidovudine therapy. All 6 affected patients required their first blood transfusion between 3 and 9 weeks after starting zidvoudine therapy, and each required 4 to 14 units of packed erythrocytes to maintain a hemoglobin level above 100 g/L over a 12-week study.” Consistent with this, Costello reported in the same year, in the Journal of Clinical Pathology that, “Blood transfusion is often necessary in patients with AIDS, especially in those receiving AZT, a drug which produces severe anaemia in a proportion of recipients. Forty nine (36%) of 138 patients treated with AZT required blood transfusion at least once.” For AIDS doctors slow to the point, Harrison’s Principles of Internal Medicine spells it out: “[AZT], used for treating [HIV], often causes severe megaloblastic anemia…caused by impaired DNA synthesis.” Even in the modern age where AZT dosing levels are now hugely reduced, in 1998, in the New England Journal of Medicine, Hymes et al investigated and reported The Effect of Azidothymidine on HIV-related Thrombocytopenia, and found again: “The hematocrit [red blood cell count] decreased in the same patients...with three of eight patients requiring red-cell transfusion by the fourth week of treatment.” So did Mocroft et al in their paper in AIDS in 1999: Anaemia is an independent predictive marker for clinical prognosis of HIV-infected patients from across Europe: “We found that 78.2% of the [HIV-infected] patients with mild or severe anaemia at baseline had received zidovudine”.

[11] In their 1988 paper in the British Journal of Haematology, entitled, 3’- Azido-3’-deoxythymidine inhibits proliferation in vitro of human haematopoietic progenitor cells, Dainiak et al reported their investigation of “the mechanism by which cytopenias develop [i.e. cell depletion, which is]…a serious, dose limiting toxicity of AZT therapy…” Observing that “Anaemia [during AZT therapy] appears to be due to bone marrow suppression [and] nearly one half of patients treated with AZT for [HIV]- associated disease develop transfusion-dependent anaemia due to bone marrow depression”, they concluded from their study that “AZT is a potent inhibitor of haematopoiesis in vitro, and that erythroid progenitors are particularly sensitive to its action. These results may explain the marrow hypoplasia that occurs during AZT administration in vivo.”

[12] AZT reaches and can destroy foetal bone marrow too. In the May 1998 issue of the Pediatric Infectious Diseases Journal, Watson et al at the University of Rochester Medical Center in New York reported the case of an HIV-negative baby born to a positive mother who had been treated with a HAART cocktail of AZT, 3TC and a protease inhibitor, suffering “high output congestive heart failure secondary to profound anemia.” The paediatricians excluded “infection, nutritional deficiencies, congenital leukemia and congenital red blood cell aplasia in the child” and considered the “cause of the life-threatening anemia in our infant…to be in utero erythroid marrow suppression by one or more of the antiretroviral agents administered to the mother.”

[13] Martin alleges that “toxicity in most cases is reversible.” This optimistic jive was flatly contradicted by Mir and Costello just a year after AZT was approved. They reported their concern in the Lancet in 1988 that “bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn. These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals.”

[14] Writing in AIDS in 1997, Kelleher et al noted, “Lack of strong evidence exists for sustained immune reconstitution by current therapies [comprising AZT and other drugs, and AZT may] unmask silent opportunistic infections.” Not only can AZT “unmask silent opportunistic infections”, it can exacerbate clinically conspicuous ones. Havlir and Barnes reported in February 1999 in the New England Journal of Medicine that HIV-positive tuberculosis patients treated with [AZT-based] ‘antiretroviral therapy’ developed “paradoxical worsening of disease…in up to 36 percent of [them], characterized by fever, worsening chest infiltrates on radiograph, and peripheral and mediastinal lymphadenopathy…[whereas] only 7 percent of patients who received antituberculosis therapy but not antiretroviral therapy had paradoxical reactions.” On 18 September 2000, Reuters released a report Doctors describe AIDS patients’ medical paradox. It could have been written by a deadpan standup comedian: “Some AIDS patients whose ravaged immune systems have been boosted by taking cocktails of powerful medicines [not even the manufacturers claim this] have been suffering a surprising increased susceptibility to infections, researchers said on Monday. Scientists at Thomas Jefferson University in Philadelphia labeled as a medical paradox their discovery that AIDS patients whose conditions had been improving [according to surrogate markers, not actual health] thanks to treatment with drug cocktails had been coming under attack from opportunistic infections that ordinarily should not have been much of a problem. In a study published [in September] in the journal Annals of Internal Medicine, the researchers said the sometimes-fatal ‘immune reconstitution syndrome’ stemmed from an inflammatory reaction by the newly strengthened immune system to bacteria or viruses already present in the patient. The researchers said the causes of the syndrome were unknown. The researchers said they were startled by the fact that the infections were affecting patients who had been benefiting from so-called highly active antiretroviral therapy (HAART) involving the use of combinations of powerful anti-HIV (human immunodeficiency virus) medicines. The doctors described learning of patients with a typical infection suffered by those with HIV - mycobacterium avium infection… ‘No one is exactly sure what to do against this syndrome yet,’ DeSimone said... More than a year ago, researchers began to see patients with HIV, the virus that causes AIDS, developing infections at times that caught them off guard. The Jefferson doctors said they decided to search the medical literature and speak with colleagues to learn whether others had seen similar developments. They said doctors at other hospitals mentioned infections such as CMV retinitis, an AIDS-related blindness...” A subject to which we will return later. In the case of children, apart from being poisonous to their blood cells, McKinney et al found that AZT didn’t alleviate their secondary infections. In their paper A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease published in the New England Journal of Medicine in 1991, they reported, “Although no control group was available for direct comparison, the improvement in the children in this study closely paralleled the observations in controlled studies of adults receiving zidovudine… Children treated with zidovudine continued to have bacterial and opportunistic infections.” Of the eighty eight children in the study, “One or more episodes of hematologic toxicity occurred in 54 children (61 percent) and neutropenia (neutrophil count, <0.75X10^9 per liter) in 42 (48 percent).” So why prescribe it? [15] Martin’s happy claim that AZT cocktails afford “long-lasting beneficial effects” was refuted in November 1997, when Lemp et al reported in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology that with HAART (Highly Active Antiretroviral Therapy), “the treatment benefit is temporary and confers no long-term survival advantages.” Obviously. How could it possibly? Would you nurse your wilting pot-plant with weed-killer? In the clever age, whatever happened to common sense? At last some lay folk are waking up; Steven Gendin wrote an article in the January 1999 issue of the AIDS-drugs-promoting rag POZ, candidly entitled If the virus doesn’t get you, the drugs you take will. He’s seen enough of his friends fade away on AZT to know. In July 2000 he went himself at the age of 34, dead of heart failure - which we will examine below.

[16] That AZT is entirely ineffective as a therapy was borne out clearly by the large-scale Concorde trials in Europe, reported by the Coordinating Committee in the Lancet in April 1994: “A total of 172…participants died [169 while taking AZT, 3 while on placebo] …The results of Concorde do not encourage the early use of zidovudine in symptom-free HIV-infected adults.” Embarrassingly for Wellcome, and disastrously for its share prices, the fabulous results of the chaotic American study that had preceded FDA approval of AZT couldn’t be reproduced. The drug was found to have no clinical benefits. Predictably, “Representatives of the Wellcome Foundation who were also members of the Coordinating Committee…declined to endorse this report” and insisted on gerrymandering the reach of its grim conclusions. Even so, the adverse implications of the trial for AZT could not be avoided. One glaring finding was that AZT’s “severe side-effects”, even in cases of patients on low doses quashed any apparent therapeutic value as suggested by raised CD4 cell-counts - about which the Committee noted that the results “also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy.” Emphasising the worthlessness of CD4 cell counting in Annals of Internal Medicine in 1996, Fleming and DeMets described it as being “as uninformative [an indication of immune status] as a toss of a coin.” Not that anyone took any notice. Today, patients terrified by their doctors’ mournful announcements of their low cell counts - still taken as a signal of collapsing health and imminent demise - are urged to start with ‘antiretrovirals’ like AZT, following which the prophesy will be faithfully fulfilled. For example, Harrigan et al reported in AIDS in July 2000 that “Triple therapy for HIVinfected patients… do not have any unique effects on CD4 cell counts independent of reductions in plasma viral load”, according to Reuters; “The data appear to contrast with recent evidence suggesting that such regimens are able to maintain an immunologic benefit even after plasma viral rebound… The team examined the correlation between CD4 cell counts and plasma viral load over 52 weeks using data from 3 randomized clinical trials… The studies compared dual nucleoside therapy with triple combination therapy that included a protease inhibitor, with or without a nonnucleoside reverse transcriptase inhibitor. The data presented in these randomized double-blinded trials suggest that the specific antiretroviral regimen used neither increases nor decreases the strength of the correlation between the change in CD4 cell count and the change in plasma viral load.” CD4 cell counting continues to the present day, as if it means anything. And the evidence mounts against multi-drug therapy, a topic deferred for a later look.

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maor, daf9:

When you are done making propaganda for AZT (at modern low doses, of course) and for HAART, and reasoning circularly, maybe we can examine the early molecular evidence that linked "HIV behavior" and AIDS. Until then, there is a LOT more data where this came from. I have already agreed with you that HIV seroepidemiology is worthless. Let's move on.

Hank: You are right about the pancytopenia, see above in [10]. Even if in vitro the action of AZT (or any other chain terminator) on mammalian DNA polymerases can be distinguished from that that on retroviral reverse transcriptase, we never know exactly how much AZT there is within any given cell of a patient, or even how evenly distributed it is within the cell. That's the difference between an organism and an eppendorf tube.

Samba

Samba,

Is there a response to Maor's comment:

"Similarly, there was no significant difference in progression of HIV disease: 3-year progression rates to AIDS or death were 18% in both groups" [from abstract of Concorde study report in Lancet]

means that HIV carriers get AIDS without AZT just as well as with AZT."

How do you explain the progression to AIDS in the placebo group?

Samba:

Would you agree that the HIV/AIDS hypothesis has not been disproven on claims of self-falsification by epidemiological data presented thus far on this forum ?

Thank you for the a priori disclaimer.

Amazing how quickly the discussion fled from the defense of the sources, numbers and graphs presented in the Single Damning Demonstration to a tangent on the evils of AZT. Anyhow...

I came up with a shorter and simpler way to express the problem with the Single Damning Demonstration after watching South Park last night.

Underpants Gnomes business plan:
1. Collect underpants
2. ???
3. Profit!

Single Damning Demonstration:
1. Plot graph of HIV prevalence estimates made by the CDC using models based on the key assumption that AIDS is caused by HIV
2. ???
3. Declare that this graph shows AIDS cannot be caused by HIV!

Perhaps someone could fill in the missing step 2 for me?

jfr writes : "How is it possible that a drug which create a deficiency in glutathione, can be a good treatement for a disease which is especially severe when the amounts of plasma glutathione are low?"

It's really quite simple.

HIV itself causes oxidative stress which as you say is bad.

AZT especially as part of a multidrug treatment kills HIV which is good.

AZT can also cause oxidative stress, which again is bad.

The question is, does AZT do more harm than good.

Check out E. J. Clin. Invest. 28, 389. It's a study of patients who've never taken antiretrovirals and shows that while NAC improves CD4+ counts it isn't nearly as good as standard antiretrovirals.

In fact there are some more recent papers suggesting that when taken with antiretrovirals, antioxidants may be helpful.