Correcting the AIDS Lies

House of Numbers - First Impressions

2009-12-04T20:37:00.007-05:00

Well, I've been busy of late, and quiet on the blogosphere, but what started out as a denialist deception has turned into a frightening assault on knowledge and public health.

I'm talking of course about the film "House of Numbers" by Brent Leung, a pretense of investigative journalism that is, in fact, a mish-mash of interview excerpts and misrepresentations that is out to promote the AIDS Denialist agenda.

Leung isn't doing this alone - a considerable amount of money is behind the effort, not only in the slick production graphics that appear in the movie, but to bankroll his travels across the globe to promote the film at festivals and universities, including my own Alma Mater, Cambridge.

And here is where it really gets me. You see, I got involved in combating AIDS denial because I frankly can't stand ignorance. If someone is wrong, I will point it out and teach them. To have someone deliberately seek out people who want to learn (i.e. students) and feed them dangerous bullshit is the epitome of evil.

A few prospective venues have stood up to Leung - who has pulled out when told he has to face reputable scientists on his panel "debate" that ubiquitously follows the showing, which actually consists of Brent saying his thing and taking questions. Journalists covering the story have apparently been asked to sign contracts to the effect that they will say that HoN is "potentially beneficial" in their article before being allowed to see the film for themselves.

Some have supported their decision to show the film based on the concept of 'freedom of speech' or a misguided attempt to 'present both sides'. However, this only holds true if there truly is more than one side, and just as Leung does indeed have freedom to tell whatever lies and misrepresentations he sees fit, the venues have their freedom not to show it.

Unfortunately we live in a media age, where spin is everywhere, and opinion outweighs fact (the popularity of stations such as Fox "News" is testament to this). We are used to interviews and cutaways that are supposed to be linked together in context, but of course the wonders of video editing mean that what we see doesn't necessarily have anything to do with how the footage was actually shot.

A case in point.

This is basically what Leung has done, although probably not to the extent of actually dubbing in additional footage. Maybe. I'm curious for example where he got the audio that accompanies the black-and-white footage where a nameless outraged man asks that the "...Press stop calling it GRID" - gay related immune deficiency. Presumably someone at the 1982 scientific conference in Washington saw fit to tape the event. In black and white. To be honest it looks more like archive footage of the League of Nations than any scientific meeting I've attended, but what do I know. Maybe I just shouldn't take that particular segment literally...but then what CAN I trust about this film?

The short answer is "not much after the first 5 minutes", judging from a preliminary viewing. One of his biggest cons is in splicing in well-known AIDS denialists between legitimate AIDS scientists as if their opinions are equally valid and all part of the same story. 17 of the scientists who were interviewed by Leung signed a letter stating that the film misrepresents their views, effectively undermining his entire premise that there is any form of internal debate about HIV and AIDS among the scientific community.

I will be addressing specific points about this film in the next few posts. I have a sincere belief that a small number of people will see this film, believe it, and acquire HIV or stop treating their infection as a result.

And it will be left to people like me to pick up the pieces.

HIV Kills T cells...and doesn't need help to do it

2009-06-08T08:45:00.005-04:00

Recently I've had cause to want to post again. Two things: an amusing comparison, and the an alarming take-over of a once-useful Society.

A certain Clark Baker (one-time cop and marine by his own account - a good reason to brush up on my Karate for self defence if ever there was one...as it also appears his 'retirement' from the LAPD may have been spurred by an assault charge made by an immigrant) has started making noise and touting the same old disproven denialist lies (such as HIV is a harmless retrovirus, originally stated by Duesberg based on Duesberg's extensive personal experience working on HIV in the lab - ie none). Baker went one step further though. Taking advantage of what sounds like fundamental apathy in the society, he managed to infiltrate the Semmelweiss Society International (SSI) with other AIDS denialists, gain control of their bank account, and throw out the non-denialist board members. The SSI's remit was certainly honorable enough - to protect medical practitioners who are wrongfully accused of malpractise, but it has certainly lost its way. The takeover is all outlined in court documents filed against Baker which I have read. This infiltration certainly explains why the SSI saw fit to 'honor' Duesberg and Farber with whistle-blower awards.

The SSI website is now filled with the slightly hysterical, ill-informed, self-grandiosing propaganda that passes for AIDS denial these days.

The sad thing is that AIDS denial is no different from the Fiber One breakfast cereal. WTF I hear you say? Consider this:

The wife here is pissed, because "everyone knows" that foods high in fiber don't taste nice, therefore since Fiber One tastes nice, it can't have much fiber in it.

This is no different from Duesberg stating that "everyone knows" that retroviruses don't kill cells, and since HIV is a retrovirus, it can't kill cells.

The Fiber One commercials are funny. AIDS denial is resposible for killing hundreds of thousands of people.

Baker, on one of his recent rants, asks for proof that HIV kills T cells. Well, I pointed this out the AIDS denialists over a decade ago, but keeping up with the literature was never a strong point of AIDS denialism (denying the current science is what makes then denialists, after all). Incidentally this bit of research also explains a comment made by Montagnier (one of the original discoverers of HIV) where he states that a co-factor, along with HIV, may be responsible for AIDS - suggesting that HIV by itself might be relatively harmless. This, if it were true, wouldn't necessarily detract from the HIV->AIDS hypothesis, but it might have had an impact on how to treat or prevent AIDS, so it was well worth looking into.

Specifically, in this 1992 paper by Montagnier, they state that

Following infection of lymphoblastoid (CEM) or promonocytic (U937 and THP1) cell lines with HIV-1 cytopathic effect was observed only in association with mycoplasmal contamination. Moreover, HIV-1 infection of U937 cells after experimental inoculation with a human isolate of M. fermentans led to pronounced cell killing. We have verified that this effect is not merely an artifact caused by arginine and/or glucose depletion in the cell culture medium. These results confirm that mollicutes, in particular M. fermentans, are able to act synergistically with HIV-1 to kill infected cells in some in vitro systems.

He had noticed that doxycycline could protect against HIV-induced cytotoxicity back in 1990. The mycoplasma detected here is a common problem in laboratory cell culture systems - they are notorious for upsetting experiments. I wonder if this notoriety came about because of results like this. It is not surprising that a mycoplasma, or some other co-factor, might be considered in AIDS causality, and the denialists are all over results like this as proof that HIV is harmless. But Montagnier only looked for cytopathic effect - i.e. what do the cells look like under the microscope. Look at this paper, from a couple of years afterwards. I'll post the abstract - basically they showed that the cell line Montagnier used (CEM in his original 1990 and followup 1992 paper) was not a pure line - it was partly CD4+ and partly CD4-. HIV can only infect CD4+ cells as that is what its envelope proteins (gp120 and gp41) bind to. It will come as no surprise to those who actually follow HIV science that in CEM lines, all the CD4+ cells get killed, but the CD4- cells grow to fill in the gaps (i.e. no cytopathic effect for Montagnier to observe).

CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains obtained from AIDS patients or seropositive individuals. The surviving cells were followed for several months in the persistently infected cultures designated 65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light and electron microscopy, immunofluorescence, reverse transcriptase assay, polymerase chain reaction amplification (PCR), nucleic acid hybridization and flow cytometry. The virus isolates induced relatively few syncytia and other cytopathic effects in the corresponding cell lines and the number of cells positive for virus expression never rose above 44%. Distinct peaks of antigen-positive cells were obtained, coincident with high levels of reverse transcriptase activity. The cultures were strongly resistant to superinfection by laboratory strain Lai, with the exception of 65870/CEM which expressed HIV antigens in up to 15% of the cells for a few days. However, cell lysis was minimal in all cases. After long-term cultivation of the three cultures, no antigen-positive cells were detected and no trace of virus expression could be observed. The remaining cells consisted entirely of CD4-negative cells. PCR analyses indicated that cells harboring a provirus were progressively eliminated from the cultures, leaving only virus-free cells. In this system, cells carrying a latent provirus survive for a limited period of time before virus activation induces cell lysis. These results suggest that at least three types of cells exist in the CEM cell line: CD4-positive cells which are rapidly killed by the virus, a second type harboring a latent viral genome after the infection and which grow normally until activation of the resident genome by external or internal signal(s), and a third type which represents rare CD4-negative cells present in the initial CEM population and which are selected for by the NSI isolates. This is the first study documenting specific interactions between NSI strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell culture.

This is a great example of how papers that apparently 'disprove' a hypothesis actually confirm it if you look at the science in greater detail.

To wrap up the story, it's well known that monocytes/macrophages like the U937 and THP-1 lines are responsible for longterm infection with HIV, the "reservoir" of infection that is hard to kill. But this makes sense - HIV doesn't deplete CD4+ macrophages to cause AIDS, so HIV wouldn't be expected to kill monocyte cell lines in the lab...unless perhaps the cultures were contaminated with mycoplasma... Maybe Duesberg was half-right.

In any case, just as Fiber One is a tasty source of fiber, HIV kills cells.

This whole story is a great example of why AIDS denialism has moved from a legitimate question-asking exercise, through inexplicable stubborness and willfull ignorance, to downright evil. When AIDS denial is touted by homophobic, ignorant, arrogant people who (allegedly) lie and steal in order to further their devastating agenda, then it's really fallen about as far as it can go.

Bennett

Disclaimer: I have never bought Fiber One, nor do I endorse them. I have however worked with HIV in the lab in short and long-term culture systems and witnessed its cytopathic effect. I use the word "allegedly"above as Baker is so far accussed, but not proven, to be a homophobic, racist, ignorant, arrogant, liar and thief. However, anyone who calls AIDS patients "a small group of promiscuous, addicted, nitrite-huffing, gonorrheal and syphilitic bath house veterans" probably needs no further said of them.

Lemaitre M. Guetard D. Henin Y. Montagnier L. Zerial A. Research in Virology. 141(1):5-16, 1990 Jan-Feb Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells.

M Lemaître, Y Henin, F Destouesse, C Ferrieux, L Montagnier, and A Blanchard
Infect Immun. 1992 March; 60(3) 742–748. Role of mycoplasma infection in the cytopathic effect induced by human immunodeficiency virus type 1 in infected cell lines.

Yelle et al Arch Virol 1994;139(1-2):155-72 "Analysis of long- term viral expression in CEM cells persistently infected with non syncytium-inducing HIV-1 strains.

Maggiore

2008-12-30T20:57:00.002-05:00

"Why did she remain basically healthy from 1992 until just before her death?" asked David Crowe,

Good question David. Perhaps because 16 years isn't too far outside the normal progression for untreated HIV infection. At 10-15 years (depending on the study) she might have been classified as a long-term non-progressor (about 10% of people with HIV do), but then only if her CD4 counts were normal, and we have no idea about that. In one long-term followup of so-called LTNP's at 10 years, by 18 years of being HIV+ 86% of those LTNP's had progressed to AIDS. The strongest individual predictor of progression rates has consisently been viral load and/or anti-HIV killer T cell responses, so even reaching one breakpoint (10 year survival) doesn't easily predict the chances of reaching another (15 year survival).

This is all hand-waving though - the only facts are that someone lost a mother and someone lost a wife, and that's terrible. My personal thoughts are that this is a tragedy that might well have been preventable. She lays the blame herself squarely at the feet of one man:

"All that changed in 1994, she said, when she spoke to UC Berkeley biology professor Peter Duesberg..."

And really, that's all I have to say on the matter. For what it's worth, I really, really hope that Robin and Charlie can find some kind of peace after this second loss. What a mess.

Message for the lawyer

2008-12-01T08:20:00.002-05:00

For the LA lawyer who tried to call me - I managed to accidentally delete voicemail with your number, and since there's more than a fair chance that someone connected to the EJ story might read this, I'm posting this up here.

I can however give an easy answer to your question - basically when I wrote the EJ commentary I was a resident physician, and according to NYS law:

"If you did not graduate from a NYS-registered or LCME- or AOA-accredited medical program, you must complete at least three years of postgraduate hospital training in an accredited residency program approved by the Accreditation Council for Graduate Medical Education, the American Osteopathic Association, or the Royal College of Physicians and Surgeons of Canada."

http://www.op.nysed.gov/medlic.htm

Since I graduated from Cambridge, England I couldn't get a NYS license until after residency - which I am now done with and my application is in the works :o)

The point though is irrelevant. In my commentary I am merely an observer and bringer of facts - the facts are irrefutable. I offer my opinion in only a few places, mostly in regards to speculation about a kidney disease that is neither necessary nor sufficient to explain the story, and in hindsight most of the findings regarding EJ's fluid in various organs can be explained by the resuscitation she recieved.

Al-Bayati on the other hand offers nothing but personal opinion and speculation, laced with a heavy dose of over-interpreted, cherry-picked literature to suit his pre-conceived idea that EJ must have died from something other than what the LA coroner found.

A side-by-side comparison of the coroner's report and Al-Bayati's report will reveal just how often Al-Bayati misrepresents it - and that's all I really did.

Conspiracy!

2008-06-20T23:03:00.002-04:00

So there isn't really much to say once the conspiracy ideas start flowing (most sensible readers will ignore anything further from that side of things), but I thought it would be fun to pose a few questions:

Who is more inappropriate to comment on medical research regarding HIV, a physician with a research background in HIV, or an online "journalist"?

Since the commentators are quite right that an "email club" couldn't possibly convince the BBC to retract their program on the ICC, is it perhaps more likely that they simply saw they had been duped once the Re-Appraising AIDS denialist group started praising the story (and they realized that the "experts" quote in the story were in fact merely AIDS denialists)?

I leave the reader to judge.

A good question

2008-06-18T21:54:00.002-04:00

Ironically this was posted by the (of late disruptive) Liam Scheff, although of course it's not his words - they are far too sane.

This was emailed to me by a non-Blogspot member. Consider:

1. Fundamental assumption: accept medicine the way it is. Therefore, your attempts to improve it are unwanted.

Who really knows how long those kids will live? Maybe all of them will die in their 20's due to ARV's? Who knows, there is evidence that ARV's prolong lives that are Th2 imbalanced, with respect to their immune system balance among Th1 and Th2 (helper T-cell inversion). The reason, the drugs depress the production of the cells that make these cytokines by killing them, and thereby abating an autoimmune condition.

But there is much evidence that these are harmful:

It has been about 7 years since it was published in The Journal, AIDS, that children born to ZDV-treated mothers "are more likely to have a rapid course of HIV-1 infection compared with children born to untreated mothers, as disease progression and immunological deterioration are significantly more rapid and the risk of death is actually increased during the first 3 years of life" [12. de Martino et al., Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AIDS. 13 (8):927-933, May 28, 1999.The Italian Register for HIV Infection in Children. AIDS, 13:927-933, 1999].

Therefore, it behooves us to think about at least improving the situation for the children involved, don't you agree?

Discussion is warranted. Can we suppress the Th1-2 population by non-toxic means, or perhaps by interference. Suppose we invent a peptide that interferes with the harmful effects of Th2 cytokine-driven storms on the tissues and especially on other immune cells (since the Payer's patches go first finally, indicating complete disruption of the lymph system).

Are we really expected to believe that there is no room for growth in medicine? Critical analysis, and then discussion regarding weaknesses and strengths in a hypothesis are required.

Whomever this is raises a number of good points. Firstly, the assumption that medicine is good enough is obviously entirely wrong. Medics and scientists in general (or let's broaden the scope to include the entire human race) have been wrong in the past, are probably wrong about some things now, and will be wrong about new things in the future. We cannot accept the status quo and expect that there's no room to improve. In the case of HIV for example, monotherapy led to dual therapy which led to hit-hard-hit-early with triple therapy, and now we're looking at monitoring and waiting until it's worth treating (if at all). Each step appeared to be the "best" approach at the time, but in hindsight they weren't the best way to go. Hindsight of course is 20/20. In another decade or so no doubt we'll look back and wonder how we managed the way we did...

The Th1/Th2 imbalance is also a feature of any chronic viral infection - HIV included. The antivirals don't actually kill off the T cells, but HIV-induced immune activation certainly does, and there is HIV-induced impaired T cell replacement. If anything the meds improve both of these actions, which is why they result in increased T cell counts over time.

The AZT study mentioned was important, although there is a large caveat in that the survival hit was in those who were HIV-infected _despite_ AZT prophylaxis. Obviously there were fewer HIV-infected kids than there would normally be without AZT. The questions that arise are: is this an effect of AZT directly? Is this because "tougher" clones of HIV made it through the AZT and were therefore worse to acquire (this would confound the results and make it appear as if AZT correlated with a worse outcome, even though it wasn't causal)? Does the AZT prophylaxis actually _select_ for more difficult viral clones? I don't think anyone yet has an answer to those questions, but all are potentially valid.

The real issue for me, and which denialists, well, deny, is that untreated HIV infection is so goddam awful in kids. Fully 25% or more will die by age 5 years. In the era of decent therapy and prophylaxis, risks of opportunistic infections and death are much less.

PEDIATRICS Vol. 120 No. 1 July 2007, pp. 100-109 (doi:10.1542/peds.2006-2052)

Could more be done - I certainly hope so, and the idea presented here about some kind of immune modulator sounds intriguing, and not the first time it's been suggested. We know that CCR5-delta32 mutations severely hamper viral replication but don't seem to hurt the human host, so if a way could be found to mimick that without buggering up the normal immune function, they why not? There is strong evidence that somewhere along the way cytokine signaling is wrong in HIV infection, and whether something abnormal needs to be turned off or something normal needs to be turned back on, it's far from a bad idea to look into that.

Further falls in my estimation

2008-01-30T06:21:00.000-05:00

Oh the irony - Liam Scheff arrives on my blog firstly challenging me to post his comments, then to reply on his own blog, and through it all taking pot-shots at my personal and professional ethics.

So I take the unusual step of actually going to his site and writing in.

And after receiving two posts which he presumably either cannot refute, or which unfortunately don't fit his perception of me as an evil Pharma-Nazi, he shuts down discussion with two further posts fading into the ether...

However, since I assumed (rightly) that Liam would do such a thing, I saved the posts for posterity. Here are the comments that Liam would rather not have on his blog, saved as screenshots of the fact that these comments were in the moderation queue while he let other posts through.

Cheers

Bennett

BBC opinion on Liam Scheff's journalism

2007-12-05T16:36:00.000-05:00

Re: Guinea Pig Kids

"Following a complaint, an investigation by the BBC's Editorial Complaints Unit has identified serious failings with this programme and ruled that some of the online material based on it was misleading."

"A correction will be published on bbc.co.uk, as part of the pages on which the material complained of appears, with a link to this summary. In addition, the ECU will contact other websites featuring the material in order to draw their attention to its ruling. The management of BBC News is addressing the issues arising from the ruling for the commissioning and supervision of independent productions of this kind."

Interestingly a private letter from the BBC notes not only the difficulty of convincing people who are inherently biased that they are wrong (i.e. AIDS denialists), but also talks about exploring copyright breaches by those who might have propagated the video online without permission.

While it doesn't fully appreciate the fact that AIDS denialists used the HIV+ foster kids at the ICC in a cynical attempt to promote their own views and pseudoscience, the findings do at least recognize that an attempt was made along those lines.

The really sad thing is that it took the BBC so long to make these statements, and in fact that the programme should never have been allowed to have been made, never mind aired. It's a shameful example of journalism of the worst kind. I've said it before, and I'll say it again. By all means criticize and comment, whether about HIV/AIDS, clinical trials, stem cell research, or whatever, but do so from a position of truth and honesty. Blatantly lying about something, or simply not telling the truth because it conflicts with your story, is simply inexcusable.

An example of how AIDS denialists are their own worst enemies...

2007-10-27T15:56:00.000-04:00

As many readers may already know, the BBC has issued an apology for the errors and bias in their story "Guinea Pig Kids", which was an AIDS-denialist inspired film detailing alleged abuses due to allowing foster kids into pediatric anti-HIV treatment studies. The facts were that the kids were faced with study medications (already proven safe and effective in adults) or nothing. These studies and others like them paved the way for current standard-of-care in treating pediatric HIV infection. No-one died as a result of the trials. A full investigation by the New York State department of health found issues only with incomplete documentation, and revealed that these were common at a national level. On that topic at least the program perhaps did a service, but that was hardly the point the denalists were trying to make.

The denialists would have you believe that not only are the meds too toxic to use (a commonly believed myth - also discussed here) but that the Incarnation Childrens Center forced the kids into "experimental" (implying "untried") treatment regimens, took kids away from their parents if they didn't comply with study requirements, and used inhumane procedures purely to enforced study drug compliance.

I was among several people who helped formulate a complaint to the BBC about this story, and I've been critical of the ringleader's "scientific journalism" for some time (a certain Liam Scheff, who is already whining about having had his masterpiece dismantled). If Liam were actually correct about any of the accusations he made he would stand to be held up an a hero. Instead he has succumbed to believing the same tired denialist lies and misrepresentations as the other dissident sheep, and thrown in a good handful of his own scientific errors for good measure, to further muddy the water of respectable scientific debate and public education.

Speaking as one from the inside, the most amusing thing is that the AIDS Denialists were to some extent their own worst enemy. After AIDSTruth complained to the BBC (and made it public they had done so) one of the core denialist groups posted a press release asking the BBC to reject the complaint! As it happens, the BBC was dragging its feet over the whole thing and we had to push to get the complaint moved up the management chain. One factor that was part of the slow move was making the point that the documentary was denialist-inspired and led. By issuing the press release ironically the denialist movement neatly proved this point for us :o)

The key points from the BBC's apology are:

Rasnick's discussion on AZT's toxicity was misleading, contrary to current medical opinion, and was not balanced by the programme makers.

The links made between loss of custody of kids (usually already in foster care) and enrollment in clinical research were unsubstantiated, in at least one case clearly false, and certainly misleading.

The claims made that antiretroviral therapy would adversely affect childrens' health were judged to be false.

The program was biased towards AIDS denialism.

Sadly they didn't uphold all complaints - specifically for me the issue where Vera Sherav asks "why didn't they provide the children with the current best treatment?". Honey, the "current best treatment" was nothing. The BBC lost the plot with that complaint, focusing instead on whether or not the children were taken advantage of due to their socially vulnerable status. In either case, their website and video clearly give the misleading impression that the studies did indeed target vulnerable children. "The experiments continue to be carried out on the poor children of New York City." ends one page. Disgusting. The BBC is supposed to be held up as an international standard of journalistic excellence and integrity - but when they do little to no fact-checking and resort to sensationalist stories for viewing figures they only serve as an example of how NOT to do good reporting.

The BBC is still arguing over what to do about this. Will heads roll? Will the video and websites finally get taken down? Discussions are ongoing "at the highest level". We'll see.

Giving journalists a bad name.

2007-10-11T18:34:00.000-04:00

The linked article sums up typical AIDS denialist thinking. You leap all over a perceived failure of mainstream science (ignoring the fact that 80% of new drug discoveries fail), drag out disproven denialist claims, quote two well-known AIDS denialists and sit back looking smarmy.

Except that the author completely failed to understand the vaccine in question and how it worked, and why it was supposed to work, and therefore based the entire article (which was a diatribe on HIV antibodies) on a false premise. I am astounded. It took me less than 30 seconds of research (I googled the vaccine name) to find that the author has misunderstood the study. Or rather, Ms Maggiore had misunderstood the study perhaps and he had believed her. Whether he did so out of laziness or out of a personal belief in Ms Maggiore's cause I cannot say, but either way it's terrible journalism.

I wrote in, and just in case my comment gets rejected, here it is anyway to explain to the average reader why the author, Maggiore and Duesberg are completely off-track.

Err, since when have antibodies been a marker of immune success, and since when have antibodies been "the problem" of AIDS?

Neither Duesberg nor Maggiore knows what they're talking about. www.aidstruth.org

And neither does the author of this article. The vaccine MrkAd5 HIV-1 is not supposed to produce anti-HIV antibodies, but instead produces anti-HIV T cell responses. The same kind of T cell responses that are shown to protect people against HIV infection and slow down progression to AIDS - as predicted by mainstream AIDS scientists but going against the theories of Duesberg, Maggoire and the like.

http://www.retroconference.org/2005/CD/PDFs/504.pdf

Please get your facts straight and stop pandering to pseudoscience for the sake of an "exciting" story. You give journalists a bad name.

Petition in Support of Ms Madlala Routledge

2007-08-13T10:16:00.000-04:00

Please go to this link and sign the petition in support of the fired deputy health minister of South Africa, Nozizwe Madlala Routledge.

Whether it changes anything or not, the more political pressure the better, and the more support the better.

South African AIDS disaster continues

2007-08-09T11:18:00.000-04:00

For those following the global HIV/AIDS epidemic, the real issues have been focused on African nations. AIDS denial, for the most part, is a luxury afforded to the West where HIV and AIDS isn't as publicly noticeable. One sad outlier of course has been the Government of South Africa.

Thabo Mbeki has grabbed the headlines for years for his bizarre failure to firstly even admit that AIDS existed, then that it was a problem and that HIV was even the cause of AIDS. Public education campaigns and the supply of antiretroviral medications have been slow to non-existent. He even refused free antiviral medication offered by pharmaceutical companies. He pulled together a "Presidential AIDS advisary Panel" to discuss whether HIV caused AIDS after reading about AIDS denial on the internet. His health minister, Manto Tshabalala-Msimang, recently touted the benefits of lemon juice, garlic and potatoes as an AIDS treatment as an international AIDS meeting, to ubiquitous ridicule from the world's scientists.

One shining star however stood up to bravely try to change the course of this sinking ship. When Minister Tshabalala-Msimang was hospitalized with what turned out to be severe liver disease, the Deputy Health Minister Nozizwe Madlala-Routledge made several key statements that suggested a possible change of strategy. However this was not without risk, and several times she apparently angered the establishment enough to have to backtrack or moderate her statements.

Most recently she attended, or at least tried to attend, an international AIDS conference in Spain. Just after arriving she was told that the formality of requesting Presidential approval for such a trip had been denied. She returned immediately without attending the event.

And Mbeki had his excuse. Today, on the eve of Woman's Day in South Africa, she was fired.

Mbeki has once again shown his true colours, as a fool with enough ego to feel bruised by an intelligent woman standing up for her country's best interests. If Tshabalala-Msimang remains in control, and if the new Deputy is either of the same ilk, or too timid to risk their job, this spells disaster for the meagre progress South Africa has made to date.

Classic Dissident Viral Load Misunderstandings

2007-07-25T23:14:00.000-04:00

I read a "quote" today from the good old denialists Andrew Maniotis

"...viral load is only able to predict progression to disease in 4% to 6% of HIV-positives studied, challenging much of the basis for current AIDS science and treatment policy" [Rodriquez B, Sethi AK, Cheruvu VK, et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296(12):1498-506, 2006;Cohen J. Study says HIV blood levels don't predict immune decline. Science 313(5795):1868, 2006. "

Of course this is related to the paper I referred to in an earlier post. As is typical for AIDS denialists, Maniotis is either unable to understand the science, or deliberately misrepresents it. He certainly "quotes" from the paper when in fact no such quote exists (it's one of his own!).

As Mellors and others have shown, viral load is actually predictive of progression to AIDS and death extremely well. In fact, in their original paper the researchers showed that this link was present regardless of baseline CD4 count. In full support of this, the Rodriguez article confirmed that in general viral load measurements were a good predictor of CD4 cell decline.

But, and listen closely, they said that absolute viral load only predicted 4-6% of the RATE of CD4 cell DECLINE. They didn't say that it only predicted it in 4-6% of patients, nor 4-6% of the CD4 cell count, and certainly didn't look at risk of AIDS or death.

In laymans' terms, if someone's CD4 cell count dropped by 100 over a year and someone else's CD4 count dropped by 200 over a year, only 4-6 of that difference of 100 could be statistically explained by having a higher viral load.

This is nothing new, as Rodriguez made clear - all the work did was quantitate the impact of one variable (viral load). Other factors would include the level of immune response, proviral load, nutritional status and even mental health (depression has been known to be linked to an increased risk of AIDS for years - similar to cancer).

No doubt this "4-6%" myth will propogate and mutate - which is why I'm posting. As I've said many times before - by all means criticize and debate, but don't do so from a position of pseudoscience.

AIDSVIDEOS

2007-05-12T23:21:00.000-04:00

I was recently pointed in the direction of a new initiative exploiting the growing popularity of places like YouTube and other online video sites.

Basically, talking heads and videos are a lot more striking than simple websites. The dissidents have (as usual) got there first with a couple of films posted online and/or in rare public viewings. This group of people have got together to create a series of counter-videos to either explain the science and medicine behind HIV and AIDS, or to counter specific dissident points.

Intentionally, their videos are titled to draw in dissidents, and apparently it works rather well :o)

This kind of work is long-overdue and should be applauded. As with this site and AIDSTruth, the work is pretty much done as a hobby, but what I've seen so far looks pretty good. Certainly a better job than I could have done!

The story continues...

2007-05-05T10:23:00.000-04:00

Apparently Andre Parenzee is appealing yet again with the Perth Group at his side.

In a statement, Eleni says "Even the expert on sexual transmission did not come up with one single study which proves that HIV is sexually transmitted. "

By that I'm assuming she's referring to Padian, whom the dissidents see as the be-all and end-all of HIV sexual transmission. And yet Padian gave multiple examples of papers showing heterosexual transmission of HIV in the rebuttal she has on the AIDStruth.org website, which Eleni (eventually) admitted in court she was aware of prior to testifying...

Who exactly needs to provide proof here, hmm? The Perth Group were clearly just trying to use poor Andre Parenzee to promote their wacky agenda in the public eye. Ms Papadopulos-Eleopulos hasn't even attended a college biology course - she taught herself biology and has done no biological research of her own! How can she possibly claim to be able to critically analyze the scientific literature of HIV and AIDS..?

Thankfully the judge had some common sense. Untrained, inexperienced amateurs disagreeing with evidence-based scientific consensus is not the same as "controversy" or "reasonable doubt" in anyone's mind but their own.

Perth Group lose court decision

2007-04-27T08:04:00.000-04:00

At last - I can feel free to comment on the case of Andre Parenzee. Having watched from the sidelines and been privy to some of the behind-the-scenes chatter, from both sides, I can at last let loose.

The bottom line - for the first time the dissidents have tried to take their views into the public realm of the legal system, and argue their case to non-scientists in an attempt to bamboozle and confuse just enough to set some kind of legal precedent in their favor. There have been urban myths about a German high court saying that HIV doesn't exist (when in fact the court papers, when translated from German, actually talk about prosecuting a doctor for malpractice and clearly side with the orthodoxy). There has even been a sad, blatantly self-absorbed, fantasy novel about taking the HIV science to court and proving the denialist cause.

But you see, here is where the fantasy world of AIDS denial is forced to catch up with real life.

Take for example one of the pivotal movements of the trial - when Robert Gallo, testifying by video phone, says something about everyone knowing that HIV causes AIDS. According to the dissidents, the judge "rebukes" Gallo's arrogant testimony by saying, "Not everyone thinks that way." No wonder then that they are surprised and invoke conspiracy theory and corruption to explain the outcome of the trial.

The truth however is rather different - when the judge made those remarks he was in fact grinning, sharing a joke with Gallo that the Perth Group were outliers to the normal paradigm.

So now the judge's decision makes more sense. It is however a telling example of how the denialists misinterpret what is in front of their faces - they were reading the same court transcripts that I was after all, but I didn't get the same impression about how it went that they did. It's no wonder that as a collective they can't interpret the science correctly either.

There were other reassuring aspects to the judge's findings. As I showed repeatedly on the BMJ forums, the Perth Group lie and twist the evidence to suit them. One particular argument goes along the lines of:

PG: Montagnier didn't prove the RT came from retroviruses, it could be confused with a cellular enzyme.

Bennett: But the references YOU supply tell me the biochemical differences between this cellular enzyme and the one Montagnier found. Montagnier's original paper also states that he performed CONTROL experiments to show that it wasn't the cellular enzyme based on these biochemical differences.

PG: No he didn't.

Bennett: Yes he did, read the bloody papers.

PG: It was oxidative stress.

Bennett: No it wasn't.

PG: Yes it was. Oxidative. Woosh. [waves hands]

Bennett: Is this getting a little like Monty Python...?

The judge agreed with my own opinion of the PG.

"Justice Sulan said Ms Papadopoulos-Eleopulos, a physicist who works at the Royal Perth Hospital, relied upon opinions of others, which she often took out of context and misinterpreted"

Overall in fact, every point they made, even down to the argument that the PG are qualified to comment on HIV/AIDS science, was rebuked.

Justice John Sulan today dismissed the witnesses' testimony, saying the pair lacked credibility and were advocates for a cause rather than independent experts.

In my own mind, the only thing left to answer is why. And I still don't know that. Having interacted with them for months on a daily basis I am convinced they are either delusional or stubborn or both. I am seriously concerned that they are knowingly lying, but that's harder to prove. They display many characteristics of sheer stupidity and yet spend hours of their time overanalyzing and misinterpreting the literature, so clearly have some form of grey matter between their ears - they can at least put together some form of argument even if its entirely illogical. What's most frustrating to me is that they are completely un-educatable and refuse to listen to the facts.

I wonder if and when they ever will. I seriously doubt this will slow them down one bit in their anti-AIDS campaign.

The bottom line is that one more sad chapter in the ongoing AIDS denialist movment is closed, at least from a practical perspective. I am sure however that the dissidents will continue to tout their views and if anything use this loss as yet more evidence for an establishment conspiracy against them. Crazy.

Official Complaint made to BBC about Liam Scheff's ICC lies

2007-01-19T20:42:00.000-05:00

Ah, someone else has taken up the torch of the ICC story. For those who aren't aware check out this post and this one on the story of how AIDS denialists managed to con the BBC into telling the story of alleged abuses of foster kids in New York City. In truth the kids were provided access to therapies already approved in adults under the protection of a formal clinical study.

It looks as if we might just maybe be able to get the whole thing retracted. Finger's crossed... Enough damage has been done already by the dissidents without poisoning the minds of the gullible further.

Drug Resistance

2007-01-12T20:27:00.000-05:00

It's been a while since I've felt the need to post much new. Dissident debate is so stagnant that it's difficult to see anything original come to light.

A recent thread opening up on AME however reminded me about the problems there that they have with censoring any kind of intelligent poster (i.e. someone educated in virology). The questions arose - how to we know HIV is drug-resistant in some people with a test, and how can a virus acquire drug resistance anyway, when that's only possible in living organisms like bacteria?

The questions underline the biologic ignorance that is fundamental to misunderstanding much of HIV and AIDS. The saddest thing is that these people largely refuse to be educated.

Let's start simple - what is a virus. A virus is basically a collection of nucleic acid (be it RNA or DNA, it doesn't really matter) which is encased in a protein shell, and those proteins are encoded by the same nucleic acid they encapsulate. Viruses may or may not also possess an envelope. Again, it doesn't really matter. The only differences that the RNA/DNA or the enveloped/non-enveloped structure cause are subtleties in the replication cycle of the virus. The bottom line is that the protein is protecting nucleic acid that is able to produce more of the same protein.

So, since they're fundamentally only protein and nucleic acid, viruses obviously lack one of the key functions necessary to perform biologic activity. Namely, the ability to create energy.

Biology is really nothing more than chemistry with a purpose - you can boil down all biologic reactions to chemistry, and indeed all chemical reactions to atomic physics if you really want to go all out! The trouble is that the natural order of the universe is chaos - the second law of thermodynamics! Biologic organisms however are inherently ordered - fat molecules are lined up, proteins fold in certain ways, cells contain distinct organelles and bodies are made up of distinct organs. In order to create this order, energy must be put into the system.

Viruses lack this ability - and so they can only replicate if they can steal some from another living organism, a cellular organism that has it's own energy-producing machinery. As such, viruses are obligate parasites (meaning they HAVE to be parasitic). In some respects they might be thought of as sea monkeys - only "coming to life" when you add the magic ingredient.

Now obviously they are additions to this simple definition. Some viruses can produce additional DNA/RNA building blocks for example, others need to steal these also. Some will only infect dividing cells (which are mass-producing the biologic building blocks) and others will force non-dividing cells to start dividing. Some viruses replicate in the cell cytoplasm, others in the nucleus. They all follow similar themes however. Ultimately a virus must bind to a cell, get into the cell, unpackage it's genome, produce new proteins and new progeny genomes, package new viruses together, and get out of the cell. The patterns of replication that often define a virus species (certainly that's how viruses used to be defined, which is why HIV for example was originally called a type-C retrovirus) will depend on the structure of the virus and the additional proteins the virus encodes.

Moving on - how can a virus acquire drug resistance. Well, the real question should be how can they NOT acquire drug resistance! I think the trouble starts with people thinking that drug resistance is some kind of pseudo-intelligent decision made by a living organism to adjust to its environment. That's plainly rubbish. Bacteria and viruses can no more decide to become drug-resistant than you or I can decide to grow wings and fly. It's simply not a "decision" we can make. What CAN happen however is that certain genetic elements can be created by accident which might result in a different set of proteins or a modification of the existing set of proteins. The 'superbug' MRSA for example (Methicillin resistant Staphylococcus Aureas, a nasty multi-drug resistant bacteria) becomes resistant from the insertion of 'new' genetic elements into its genome. Now, I'm not saying that the genetic elements are literally "new", that SA suddenly creates a whole new set of genes to become MRSA, but in the context in which they cause a problem for us they are new. What most likely happened is that these genes envolved over millions of years in bacteria to protect them against toxins produced by fungi, viruses, or other bacteria. When we come in with our antibiotics (which are usually derived from natural compounds!) we cannot be surprised if mother-nature shows us what is up her sleeve.

Another example is the growing number of streptococcal infections that are drug resistant - in this situation the protein that is exploited by us to carry the toxin penicillin into the bacteria mutates subtly so it doesn't bind penicillin very well. Sure, they means that the bacteria has a slightly dodgy protein now - but faced with using a less-than-perfect protein or being dead, most bacterial colonies will end up containing an awful lot of less-than-perfect bacteria. It's plain and simple Darwinian Evolution.

So when we talk about the "spread" or "creation" bacterial drug-resistance, we are really only talking about the selection of pre-existing drug-resistance strains from a mixed population. It's a little like using a magnet to pull out iron filings from sand. If you kill off all the drug-susceptible bacteria then the drug-resistant ones will survive and grow to replace them, but it will appear to human eyes as if the population of bacteria somehow "acquired" or "developed" drug resistance. The bottom line - drug resistance was probably there all along, but we've just given the resistant bugs a chance to out-compete their cousins.

Here's a visual representation: x's are normal, o's are resistant.

xxxxxxxxxxxxxoxxxxxxxxxxxxxx = normal population

o = population after antibiotics

ooooooooooooooooooooooooooooooo = drug-resistant population ("acquired" drug resistance)

Viruses have one advantage and one disadvantage when it comes to drug-resistance, compared to bacteria. Firstly a single virus can create many hundreds or thousands of progeny virions. So their replication copy-number is huge. You have lots of room for error, because so long as you get a few working models the species stands a chance of survival. The disadvantage lies in that virus genomes are incredibly tightly packed - there isn't much room to add new, potentially advantageous genes. If a virus capsid is big enough to hold 10,000 bases of DNA, you can't expect it to work very well with an extra 5,000 bases of drug-resistant gene inserted! As a whole viruses are incredibly efficient with their nucleic acid - they have very little if any junk sequence for example (we on the other hand are 90% junk DNA) and may even use the same sequence to code for 2 or 3 different proteins! As such, viruses are typically forced to use simple point mutations, small deletions, or other minor changes in order to have any kind of genetic change. You're basically creating a vast batch of new viruses, and rolling the dice each time.

Aside from having large number of progeny, viruses are also inherently error-prone. RNA viruses in particular have no error-correction mechanisms in place. They rely on the base-pair matching between two strands of RNA, but if a mistake is made they have little to no recourse to correct it. Our own DNA replication on the other hand makes use of a veritable army of proteins to detect and repair DNA mismatches. Some DNA viruses may make use of this machinery as well of course, but HIV is an RNA virus.

The protein HIV uses to replicate itself (a cellular protein called RNA polymerase II) has an error rate of 1 in 10,000. HIV is around 10,000 bases long. So, on average, each HIV genome will contain one error - one deviation from the original template. HIV also uses its own protein reverse-transcriptase early in the life cycle, and that too has no error-correction mechanism. All in all this is a superb setup for creating a mixed population of viruses, of which some MIGHT, by chance, be drug-resistant. In addition, this error rate explains why many virus particles are non-functional -they are defunct genetically. It's important however to note that certain changes are better tolerated that others. A change to the cellular binding protein is very poorly tolerated (if the virus gets into the wrong cell type, or no cell at all, it's stuffed!) which is why antibodies to things like specific portions of the Env protein are consistently found in people with HIV. On the other hand subtle structural changes in the scaffold of the RT enzyme can be better tolerated to avoid binding to chemical X while still allowing chemical Y to bind (which is basically how mutations in RT exist to prevent drug binding while still allowing replication to go ahead). The alleged "inconsistencies" in the biology of HIV touted by the dissidents are very simply explained by the constraints of biology and Darwinian selection.

In the case of HIV, drug resistance is very well understood. For example, just like the penicillin-binding-proteins in strep, HIV protease and reverse-transcriptase can become modified so that it doesn't bind to the protease or RT inhibitors. Some of these mutations are very specific. The first mutation described, to AZT, was in a particular portion of RT. If you then exposed the virus (in tissue-culture) to a different RTI then this mutation reverted back to wild-type and a new mutation appeared. It seemed as if the virus could easily cope with one mutation or another, but not both. This was the basis behind using more than one drug at a time to combat HIV - and it worked. The virus took much longer on average to adapt to resisting two drugs that just one alone. Remember that this is all down to chance - and, on average, it will take longer to roll "all sixes" with 4 dice than with 2, right?

And that's assuming all things being equal - if successful, antiviral therapy can shut down replication and therefore should slow down the rise of resistant strains - rolling the dice every few minutes say, instead of every few seconds.

The beauty now with modern HIV care is that so many papers have been published linking specific mutations found in the HIV genome with drug-resistance. We can say with a large degree of accuracy, that if a virus contains mutation X it will be resistant to drug B. Some tests still rely on actually trying to grow a patient's virus in the presence of various drugs (after all, we can't yet know ALL the possible resistance mutations and combinations!) but genotype testing, as it's called, is extremely useful.

And this is an important point missed by the dissidents (no doubt because, as this AME thread shows, many of them simply don't understand the fundamentals). If HIV were a crock-of-shit, if the drugs really weren't attacking it, if the drugs weren't shutting down viral replication, how on earth do they explain the rise of specific mutations in response to exposure to a drug that are associated with improved viral replication in culture, AND as judged by viral load and CD4 count in real living people. The model is its own control - the scientists are not speculating that the virus is mutating around the drugs, they are seeing it with consistent, reproducible, predictable changes in the genetic code of the virus associated with real laboratory and clinical data. Genetic changes are inherently random - any kind of pattern is meaningful.

And this is the basis behind this new test the thread was kicked off by. If you look using sensitive techniques for drug-resistance genetic sequences, you will find even the rare viruses in the population that are, by luck, rolling sixes. You can therefore save the effort of killing off the non-resistant strains only to have the resistant ones pop up - you can select a different set of drugs that will attack all of them.

So, that is how a virus can acquire drug resistance, how you can test for it, and why it's meaningful in the case of HIV. It's also, incidentally, one part of the irrefutable science proving that HIV causes AIDS.

Funding conflicts and AIDS denial

2006-11-19T09:23:00.000-05:00

Interestingly enough (considering the recent NEJM editorial discussing serious financial conflicts of interest involving recombinant activated human protein C use in sepsis management) Christine Maggiore's team is trying to discredit my Al-Bayati rebuttal on the grounds that I recieved pharmaceutical funding for my PhD.

This is true, but it’s cleverly worded to avoid the embarrassing fact (that he admitted to me [David Crowe] in an email in December, 2005) that “I was funded, on paper, by Astrazeneca for my PhD”.

Also interesting is that clearly the writer is the same person who posted my 'private' emails with Casey Cohen online, as I've only been asked to clarify my financial-interest statement by one person. David, how disappointing.

But it's crazy. The truth (which is naturally omitted from my quotes at the EJ site) is that AstraZeneca paid money to the medical school, along with a dozen or more other sponsors, and the medical school allocated the funds equally and at random.

The true quote, which I hope David corrects for Ms Maggiore is:

"It's a matter of public record (ie. Google!) that I was funded, on paper, by Astrazeneca for my PhD. Technically they simply gave the money to the clinical school and they allocated it amongst the students - Astrazeneca didn't know me from Adam."

As I state here, I have freely admitted to this non-conflict of interest funding for years in my debates on misc.health.aids. There is no secret. It's sad that I even have to write this entry to inform the people who are lied to by the dissidents. It's also sad that I have to keep records of all my dissident correspondance in case issues like this ever come up.

But that is the real reason to post this comment - to point out, yet again, how the dissidents will lie by omission, spin the truth, and also resort to personal misrepresentation to make their point. Why would the dissidents even need to delete key statements from their quotes if their arguments stood on their own merits. If they are lying to their audience about short email correspondance, what on Earth do you think they are doing with the scientific literature!!?

I get paid now over four-times as much, in terms of purchasing power, as I got in funding from my PhD stipend. I fail to see how an annual stipend of 10k (my sole source of income) which ran out about three years ago can possibly affect my judgement today.

It's also amusing to see in the same entry that Al-Bayati has known about my report for over 6 months but has yet to make any attempt to rebut or correct my statements. His latest feeble attempt (brought to my attention by Ms Cohen) doesn't reference my own report, and on that basis alone means it isn't worth replying to. My comments still stand - his analysis is flawed.

He can of course also lie to rebut it, but that's all he could do. If I was wrong in saying that PCP is a difficult diagnosis to make clinically, that EJ's autopsy report doesn't mention evidence of inflammation and consolidation, that the brain lesions are characteristic of HIV encephalitis even without p24 staining, and that the lung lesions are diagnostic of PCP and not just pneumocystis carriage, then he is free to lie to contradict me.

Dissidents stoop to new lows

2006-11-07T22:31:00.000-05:00

A recent person claiming to be called "Casey Cohen" has been spending some considerable time recently trying to get me more deeply involved in the sad case of Eliza-Jane Scoville's death. Aside from trying to organise a live radio debate with Christine Maggiore herself, pick my brains about my personal thoughts on Al-Bayati's case, and even meet up for lunch (!) she has been diligently sending our correspondance to other dissidents for online publication.

Now, this was sadly expected and I wrote my emails back to her accordingly. Still, it is upsetting to be proven right. "Casey" of course screwed it up from the beginning by writing to me from Christine Maggiore's email account. Woops. And the syncophantic babbling was getting to be a little too amusing to take over my afternoon coffee without spraying it over the computer keyboard.

Of course, whatever the outcome the dissidents 'win'. If the orthodoxy debates then we legitimize their argument. We run the (obviously) very real risk of being quoted and misquoted online behind our backs. If we refuse to debate then they tout this as the orthodoxy being closed-minded. The sickening thing to me is that "Casey" is clearly either someone very close to Maggiore if not Maggiore herself, and yet says in her emails to me that Maggiore would be "lucky to get out of the building alive by the end of the discussion" and we would "annihilate them!!". I find it extremely saddening that the orthodoxy has never once used the tragedy of EJ's death to attack Christine Maggiore, and yet we're accused of it all the time, and here are the dissidents playing on the very same topic. Frankly speaking, it's f*&king disgusting.

And note please that this person, apparently one of the "People who question the theory that HIV causes AIDS causes Death" makes repeated claims that she is on "our" side in a transparent attempt to dupe me into getting involved.

This webpage should be held up as yet another example of how low the dissidents stoop in their tactics, when basic logic and irrefutable facts stand in their way.

Of course the real test will be if they remove the website out of embarrassment (but don't worry, I made copies ;-)

More viral load analysis

2006-10-06T21:29:00.000-04:00

A recent discussion online made me perform a little back-of-the-envelope math on viral loads. As shown in the recent paper discussed below, on an individual basis the predictive value of viral load on any one individual's rate of CD4 T cell loss is poor. In fact the authors found it responsible for about 4-6% of the variation. But they also supported the original data showing a good correlation between subgroups of viral load and rate of CD4 T cell loss.

But how good?

Well, I performed the same kind of analysis on the subgroup data.

For those with viral loads under 500 I used a value of 250, for those between 500 and and 1000 I took 750, etc. I graphed the log10 value of these viral loads against the average CD4 T cell loss given in the paper for these subgroups.

The result?

A whopping 93.5% link between the subgroup viral load and rate of CD4 T cell loss. Just a tad better than the 4-6% for the individual data points.

The upshot of this? Well, clearly the paper is still saying that at the individual level the predictive value of viral load is very limited - but the SAME ANALYSIS performed on the bigger picture clearly shows why clinicians and scientists the world over concluded that viral load was a good predictor of T cell decline.

It should also but a sock in the mouth of any dissidents who say otherwise.

I'll freely admit that this analysis is far from the comprehensive dataset looked at in the paper by Rodriguez et al, but it IS the same data ;-) Regardless of its limitations, it's pretty striking.

Viral load paradigm shift? Not really.

2006-09-27T23:18:00.000-04:00

An interesting study came out recently (I managed to get a copy of the article from one of the authors) on the predictive value of viral load. It's well known (at least among those who bother to read and understand the literature) that those people with higher viral loads tend to progress faster, as was shown by John Mellors back in the mid 1990s using the large Multicenter AIDS cohort study (MACS).

This study took things one step further. They replicated the original findings of Mellors by showing again that viral load roughly predicted how fast AIDS occurred in another large cohort composed of people from 3 seperate study sites. For example, in this new paper people with viral loads less than 500 had an average loss of CD4 cells of 20 per year whereas those with viral loads over 40,000 had an average loss of 78 a year (with a smooth change for values inbetween). Basically this data proved that viral load was a reasonable predictor of rate of progression! They compared this analysis with the original MACS cohort and it looks practically identical!

But then they tried to look at the individual rate of progression of each member of the cohort. Unsurprisingly they found that the rough-and-ready estimates of progression rate within a subgroup varied from one individual to another. When they ran complex statistical analysis on the effects of viral load on THIS data they found that only about 5-6% of the inter-individual variation can be explained by the initial viral load. In another words, while viral load predicts that you WILL lose CD4 count, and you can give an AVERAGE loss of CD4 cells per year based on that count, you can't say for sure what the ACTUAL loss will be for any one person very accurately.

Well, duh. Nothing amazing there.

Now, what's sad about this whole thing is that is appears as if the dissident websites have jumped all over the mass-media coverage of this without bothering to read the paper. They are assuming that this somehow negates the usefullness of viral load measurements. Ironically if a paper showing that viral load predicted 100% of the CD4 T cell loss (an impossible thing) relied on complex statistical analysis I'm sure they wouldn't accept it with anything like the same level of naivity!

This is nothing new - we've known for years that various other factors can play into AIDS progression, from nutritional status to immune makeup, depression, and viral genetics. We've known for years that overall T cell losses include uninfected as well as infected cells, that immune hyperactivation leads to apoptosis but a lack of renewal - both things that are only indirectly due to HIV infection, but not direct cell killing. What we haven't done before is put a number on anything - to say roughly HOW much influence these things can have on an individual level.

It should also be noted that this should lay to rest any idea that mainstream science is simply laying back and accepting the current paradigm without question. If that were the case, why was this large, comprehensive, complex study performed? Is it because that when dissidents say that scientists ARE sitting back on the current paradigm they are...*gasp*...lying??! And, SHOCK HORROR, this was supported by an NIH grant, the very same NIH that the dissidents are trying to claim is horribly corrupt and under the thumb of pharmaceutical sponsors!

Ahh, is that the sound of cherries being picked?

Anyhow, I will quote from the paper:

"Our findings confirm previous observations that the magnitude of HIV viremia, as defined by broad categories of presenting HIV RNA level, is associated with the rate of CD4 cell loss and
extend this observation to patient populations comprising both men and women."

In other words, viral load predicts rate of progression to AIDS.

If the dissidents are trying to twist this paper to say anything else, they are managing a feat of astonishing deception. Is there more to the story? Of course! No-one, except the dissidents, is saying anything else. They also state that "In humans, the predictive value of immune activation level on HIV disease course, independent of plasma HIV RNA levels, can be demonstrated even when measured during early infection", which goes back to what I said above.

And I refer the reader to my older post on HIV pathogenesis.

It should also be mentioned that viral load isn't used as a clinical criteria for starting treatment unless the load is very high and the CD4 counts are equivocal. Viral load is almost exclusively used for monitoring response to therapy on the individual level, so inter-individual variability isn't an issue anyway.

This result is very important in that it highlights the need to investigate other factors important in triggering or controlling rate of progression to AIDS, but it won't really change the current paradigm in terms of understanding AIDS pathogenesis, nor will it change current treatment guidelines, because neither depends on the idea that HIV viral load is the be-all and end-all of AIDS.

Except of course, that it is in the minds of the dissidents.

Which is (one reason) why they're wrong.

More ignorant dissident ramblings about Padian

2006-08-15T18:02:00.000-04:00

I'm astonished, although I shouldn't be, that the dissident fold has not only tried to rebut the Padian article on AIDStruth, but has done so by simply repeating the same tired lies, and indeed with some of them not even reading the Padian article...!

A quote from the Barnesworld site:

"Padian could be an outlier, but are there other epidemiological studies that show higher rates of transmission?"

Oh my God.

Padian did indeed find transmission events, just not in that specific study. She quotes several papers outlining HIV transmission risks, some of which she herself was involved with. One of them documents infection risk of up to 20% per exposure!

Downs AM, De Vincenzi I. Probability of heterosexual transmission of HIV: relationship to the number of unprotected sexual contacts. European Study Group in Heterosexual Transmission of HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Apr 1;11(4):388-95.
Wiley JA, Herschhkorn SJ, Padian NS. Heterogeneity in the probability of HIV transmission per sexual contact: the case of male-to-female transmission in penile-vaginal intercourse. Stat Med 1989;8:93-102.
Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC; Rakai Project Team. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001 Apr 14;357(9263):1149-53.
Ellerbock TV, Lieb S, Harrington PE, et al. Heterosexually transmitted human immunodeficiency virus infection among pregnant women in a rural Florida community. N Engl J Med 1992;327:1704-9.

Hunter DJ. AIDS in sub-Saharan Africa: the epidemiology of heterosexual transmission and the prospects for prevention. Epidemiology. 1993 Jan;4(1):63-72. Review.
Venkataramana CB, Sarada PV. Extent and speed of spread of HIV infection in India through the commercial sex networks: a perspective. Trop Med Int Health. 2001 Dec;6(12):1040-61.
Adimora AA, Schoenbach VJ, Doherty IA. HIV and African Americans in the southern United States: sexual networks and social context. Sex Transm Dis. 2006 Jul;33(7 Suppl):S39-45.
Latora V, Nyamba A, Simpore J, Sylvette B, Diane S, Sylvere B, Musumeci S. Network of sexual contacts and sexually transmitted HIV infection in Burkina Faso. J Med Virol. 2006 Jun;78(6):724-9.

Do these people even bother to read what it is they're criticising? Also I hear repeatedly the myth that these couples were followed for 10 years. THAT IS FALSE!

It was a 10 year study but, on average, the couples were followed for less than 7 months each.

Yes, less than 7 (seven) months each.

442 couples, 3000 couple-months of data, 6.8 months per couple. It's staring them in the face. Would 10 years of no seroconversions in a huge study be interesting? Sure. But that would be over 53,000 couple-months of data. 6-7 months of no seroconversions, in a study population told to use condoms and practise safe sex, is that interesting? Not really. It just says that prevention works. Padian herself says that "The sentence in the Abstract [about no seroconversions] reflects this success -- nothing more, nothing less."

I see from the comments at Barnesworld that many are suggesting the article is mere "info-ganda", which ironically is precisely what the dissidents use to spread their ideas. The sad fact is, for many of these dissidents, that these are plain simple truths supported by solid evidence that cannot be refuted. HIV is spread sexually and causes AIDS. In comparison the dissident myths are a house of cards and, as this site and others repeatedly demonstrates, it comes down with the slightest breeze.

Fixed error - confirmed data 8/21/06

Dissident lies about Padian laid to rest at last

2006-08-08T14:55:00.000-04:00

The 1997 paper by Nancy Padian (Heterosexual transmission of human immunodeficiency virus (HIV) in Northern California: results from a ten-year study) is often selectively quoted by dissidents in an attempt to convince their readers (and perhaps themselves) that HIV is not transmissible through sex. They quote a single line from the abstract, without taking the time to read or comprehend the actual study aim:

"Over time, the authors observed increased condom use (p < 0.001) and no new infections."

But the point of the paper wasn't to see if HIV could be sexually transmitted - that was already known! The research was aimed at showing that with counselling HIV transmission might be stopped, and it was.

There are several studies that show that HIV is transmitted through sexual intercourse, with increasing risks for oral, vaginal and anal sex respectively. Examples include

Downs AM, De Vincenzi I. Probability of heterosexual transmission of HIV: relationship to the number of unprotected sexual contacts. European Study Group in Heterosexual Transmission of HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Apr 1;11(4):388-95.
Wiley JA, Herschhkorn SJ, Padian NS. Heterogeneity in the probability of HIV transmission per sexual contact: the case of male-to-female transmission in penile-vaginal intercourse. Stat Med 1989;8:93-102.
Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC; Rakai Project Team. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001 Apr 14;357(9263):1149-53.

In a move that is highly unusual, Dr Padian actually took the time to respond directly to the dissidents who are misrepresenting her work, and suggesting that Padian herself is either tactitly acknowledging that HIV cannot be transmitted sexually, or that her work is ignored by the mainstream in our "ignorance" of the science.

Dr Padian demolishes both those suggestions in this article at AIDStruth.org.

It's about time that a researcher who's work has been so abused by the dissident camp stood up for what it actually meant and put something, however succinct, into print so that the issue can be dropped once and for all.

Causing Offense - why should PR matter?

2006-07-31T09:48:00.000-04:00

I recently managed to offend someone who emailed me asking for questions. Not intentionally, but poorly chosen words written out of frustration aren't any less upsetting. I shan't mention any names, he knows who he is, and for causing that upset I feel I must publicly apologise.

But why should this actually cause me to feel upset at myself as well? Aside from generally feeling a heel for causing another human being to think less of me, it's probably tainted any chance of him taking on board my responses to his questions. And it was clear to me that however much he knew, he (a) was offended when I tried to teach him what he already knew (which he didn't tell me he already knew) and (b) wasn't all that interested in accepting the fact that some of what he thought he knew, he didn't. He wasn't an AIDS dissident by any stretch, but someone with a brain on their shoulders who wanted to understand more, albeit with a large chunk of preconceived ideas and dislike of AIDS scientists/doctors in general, and certain specific individuals.

The Dissident movement has for some time been ahead of the game with PR - the ability to reach the laymen. Even Duesberg's scientific literature is massively oversimplified and dumbed down in order to make sense to the lay reader. Key concepts such as "antibodies mean the infection has been fought off" are easy to sell, even if they're lies. The reader not only feels that they have been informed of something, but it's easy to remember, and in their own mind instantly catapults them to the standard of a PhD in immunology. They feel able to criticise the scientists, for example, for failing to take into account whether HIV PCR cross-reacts with human sequences, not knowing that, of course, this was not only thought of even before the test was developed, but is controlled for in every HIV PCR reaction of human tissue.

Books and popular magazine articles have been written from people like Maggiore, Scheff and Farber, while the orthodoxy write academic papers in journals that are hidden in medical libraries or behind expensive pay-per-view web portals. The dissidents have also had a large online presence for years, in fact many of the sites suffer from not being updated with more recent literature - most likely because it would contradict their stance. The orthodoxy has only recently managed to respond with organized efforts like AIDStruth.org and here at AIDSmyth. The simple fact of the matter is that most of us working in the field have far better things to do with our time! The other thing is that, to scientists, PR is worthless. You simply have to tell someone the truth, show them that it is the truth, and you're sorted. How you package it is irrelevant. Sadly that isn't the case in today's society of soundbites and spin. As orthodox scientists trying to educate the masses, we almost find ourselves having to pre-empt Dissident spin by hunting down potential articles that can be misconstrued and preparing to counter them. What a waste - to have to retell the story simply because someone misunderstood it. This particular person made several important comments about the fact that as orthodox scientists, much of what we say gets ignored simply because of the way it gets said. Which to me would be laughable if it weren't so sad. I would say though, from bitter experience, that if we are to get through to the fence-sitters, or even to show the dissidents that they are horribly, dangerously wrong, then we too need to learn the art of good PR.

Most of the orthodox sites from places like the NIH aren't specifically aimed at counter dissident arguements, which need to be targeted at individual dissident myths rather than simply stating standard healthcare advice and information. And of course they suffer from being part of "the AIDS establishment" and therefore corrupt and worthless.

I'm reminded of the double-bind Brian found himself in, in the movie "Life of Brian".

"I'm not the messiah!"
"Only the messiah denies his true self!"
"Oh alright then, I AM the messiah!"
"He IS the messiah!!!"

If you believe the PR hyperbole, then how can the orthodoxy win? Which should make you ask yourself, if I take away the PR, then what difference does that make?

Next time you get a cold sore, or a shingles outbreak, or meet someone with hepatitis B or C - ask yourself if antibodies really are a sign of a cleared infection, or if the dissident camp maybe, just maybe, don't have a clue. And also ask yourself why they are working so hard to win hearts and minds, when surely the truth should be self-evident.

And a point to make to the orthodox crowd reading this - we do need to watch how we say things. Not just in terms of giving the dissidents an intellectual crack to get into (which we then have to spend time filling) but in terms of professionalism and full-disclosure. This guy's biggest gripe was that the docs implied that (say) viral load measured whole infectious virions, when of course it doesn't, as detailed extensively here. Again it doesn't matter if the intent is to mislead or not, if the perception is that it is. Communication is a two-person thing, speaker and listener. Misunderstandings are often as much caused by one as by the other...

Version 2.0

2005-12-13T12:41:00.000-05:00

Version 2 of my report is being very kindly hosted by Trent again.

I have taken advantage of the publication on the ABC news website of the LA coroners report to directly compare some of what Al Bayati claims it contains to what it actually contains.

The Coroners report is hosted here at Ratbags.

I hope that by comparing the two one can come to a reasonable conclusion.

Eliza Jane

2005-11-29T18:59:00.000-05:00

I mentioned in responses to a prior post that I wasn't wanting to weigh in on the debate and controversy surrounding the sad death of Eliza Jane, daughter of the well known dissident Christine Maggiore. At that time nothing was known, nothing had been said other than hearsay, and frankly it was entirely inappropriate to do anything.

Then the pathologist's report came out, blaming her death on an AIDS-related pneumonia ( I assumed PCP or CMV pneumonitis or somesuch for that kind of statement to be made ). I still held my tongue, as without knowing the facts there was still nothing to be said.

But recently dissident Dr Al-Bayati has put in his four-penn'orth, presumably at the urging (hiring?) of Christine to counter the autopsy report. His report is terribly, terribly flawed.

In response I wrote my own report. I have nothing to say about Christine other than to extend my sincere condolences (as I have done already). This has nothing to do even, really, with EJ as a case. As you'll see, my report mostly deals with the evidence Al-Bayati uses in his arguments and how flawed they are.

My report has been very kindly hosted here by Trent McBride.

There are other rebuttals out there as it happens, some from other scientists or physicians, some from people who simply have a head on their shoulders and some common sense. I don't claim to have written anything special. But I simply couldn't stand by and let the misinformation of Al-Bayati go without responding.

Antivirals

2005-08-17T22:58:00.000-04:00

This guy Wilhelm is a supposed virologist, but in the discussions I've seen he's at best half-educated in the field.

Firstly he makes the old mistake of assuming that the nucleoside analogues (RTIs like AZT) are DNA chain terminators primarily. They are not, they are reverse-transcriptase inhibitors primarily, and they act by chain termination. Am I nit-picking? No - and here's why.

You probably have a car right? You probably use a key to get into and start your car, right? Does your key work on your neighbour's car? No? Why - because it fits only your car.

The same is true of drugs like AZT, they cannot possible act on a DNA chain unless they are placed in position and chemically altered to join the DNA chain. The positioning and altering is done by enzymes like HIV reverse transcriptase (RT) and cellular DNA polymerase. AZT doesn't fit DNA polymerase. AZT does fit RT. This can be shown in chemical assays and in tissue cultures - AZT and other similar drugs are many more times effective against the virus than against the cells (some cross-reactivity with cellular enzymes is almost inevitable, but even here AZT isn't even the worst...!)

So not only will AZT not work to chain-terminate unless HIV RT is present, it will ONLY work on the DNA chain that is linked to the viral enzyme! So antiviral drugs like AZT are very specific to the virus, and act directly against it.

Wilhelm speaks as if AZT acts on the proviral DNA. It can't possibly do that, because by the time the provirus is there, reverse-transcription has already finished. The only way you can reduce proviral load is to kill off infected cells. The Perth Group in fact try to argue this same point in their anti-AZT critique and state the obvious - if you close the stable door when the horse is in the pasture you can't reduce the number of horses in the pasture... Stupid bastards.

He's also obviously ignorant that the protease inhibitors were the first "designer drugs", drugs that were designed on a computer to chemically match the target enzyme (the viral protease) rather than any other similar enzyme. These drugs are the best example of virus-specific drugs out there! Viruses do indeed use the cell's machinery to replicate, but many viruses also carry their own essential enzymes that aren't found in the cells. HIV carries three of them, of which two are currently attacked by drugs (reverse transcriptase, protease, integrase). It also has several accessory proteins that aren't enzymes but are essential for HIV to replicate. These too can be targetted, at least in the lab. The most important two are called Tat and Rev. They may become future drug targets as well.

His comparison between bacteria and viruses is absurd. Bacteria do mutate, but their mutations are also completely random. What they do which many viruses do not is acquire large chunks of new DNA in the form of plasmids. These can spread antibiotic resistance very easily, even between different species of bacteria. Bacteria can no more "adapt" to a new environment than we can. Do we grow gills when we're drowning? No. But if you hand us a snorkel or scuba gear we can do quite well! Antibiotic resistance plasmids are the bacterial scuba gear.

All mutations are random, in bacteria, viruses and human beings. Viruses in fact are far superior to bacteria in the rate of mutation at the nucleotide level because they replicate at far higher rates. When you have several thousand progeny, it doesn't take many rounds of replication to come up with an advantageous mutation such as a drug-resistant enzyme. The defective viruses will die, and in the face of drug therapy so will the neutral viruses, leaving only the resistant ones. It's called Darwinian selection - survival of the fittest.

If a resistant bacterial colony appears on an agar plate it is not because the bacteria "developed" resistance, its because among the bacteria that were present all the non-resistant ones died off, leaving the resistant one to take over.

What is most striking is that you can these days predict which drugs HIV is resistant to by sequencing the virus from each individual patient. This feat alone should be impossible if HIV didn't exist, not least because why would the same mutations always appear with the same drug-resistances? People with HIV these days can change drugs with the knowledge that their HIV is NOT resistant to the new one, whereas in the old days it was mostly trial and error. You can correlate drug resistances to treatment success or failure - again, this makes no sense if the virus is meaningless and the drugs non-specific. This simple, common practise every day in HIV clinics all over the world, disproves the dissident views on so many counts.

Not least the views of this guy, apparently the closest thing they have on the forum to a scientist. I wonder what he would think of Aciclovir acting against herpes viruses....

Latency Confusion

2005-08-15T10:49:00.000-04:00

I've noticed a lot of confused/conflicting posts over the last week or two regarding the old doozy of HIV latency. The concept isn't helped by the fact that the word has two meanings, and BOTH apply to HIV and AIDS. One article talking about latency may have nothing at all in common with another. The difference is explained during undergraduate virology classes, but since so many of the dissidents are either untrained or deliberately choose to mislead their readers, this makes excellent fodder for anti-HIV "logic".

Clinical Latency
HIV infection has a well known asymptomatic period, in between the seroconversion illness (which doesn't always happen - 50% of the time) and end-stage disease (AIDS, which nearly always does happen - 95% of the time). This period is known as clinical latency, because clinically (meaning, in terms of wellness, signs and symptoms) there isn't much going on. Generally speaking, only lab tests will give a hint that something is amiss, such as depressed CD4 T cells, and of course virus-specific tests like antibodies and viral load.

However, it is now well established that during this time "the virus" is replicating at a significant rate. This rate is reflected in the amount of virus in the peripheral blood, the viral load. Although the virus replicates in lymph nodes, of course some gets out into the blood, and this can be detected using standard tests like RT-PCR (the RT bit refers to the fact that the virus is made of RNA, and so as to be converted to DNA for the PCR to work). If the virus were dormant then there would be no viral load. The only reason why the infection doesn't become run-away is that the immune system is able to partially control it. Contrary to popular dissident belief, it is not due to antibodies. As with most viruses, it is the CD8 T cells than control the infection. In an ideal situation the CD8 response would be able to clear the infection, but HIV has the ability to persist. That ability is tied into the following:

Virological Latency
Now, on the level of the individual infected cells, some will NOT be producing viruses. And by producing viruses, we're talking thousands at a time. Viruses do not replicate by multiplying, like bacteria, or through offspring like sexual animals or plants. Rather they literally turn an infected cell into a virus factory. One virion can result in thousands or millions of other virions, depending on what virus we're talking about. This is required because we know that not all viruses are active, in the case of HIV it might only be 1 in 60,000 peripheral viruses - the others are either genetically defective or physically damaged.

Because HIV has the requirement for cellular transcription factors (NF-kB specifically) if that protein isn't around, it won't do anything. The provirus will be latent. This is virological latency, and is found also in herpes viruses. However, since in a population of many millions of T cells some will be producing NF-kB, say in response to a pathogen they recognise, not all the proviruses will be latent.

The analogy is perhaps a snowstorm on a TV screen. Some of the dots are white, some are black. Overall the image is a grey fuzzy mess! It doesn't mean that each virus is "half active", in fact there is good evidence that for HIV it really is an all-or-nothing response. Either the provirus is shut down, of it's fully active. Black, or White.

So when you hear people talking about "reactivating latent virus" they're referring to turning all the black dots white. When they're talking about "HIV replicating throughout infection" they're referring to the fact that it's a snowstorm rather than a black-out. As a virologist, this makes perfect sense to me, because comparing clinical and virological latency is like comparing chalk and cheese. Sometimes they might coincide (e.g. herpes breakouts) but there is no logical reason why they MUST coincide. The two concepts are not contradictory or confusing, although it's easy to see how they might be to some people!

More Lies from Liam Scheff

2005-07-29T13:58:00.000-04:00

Liam Scheff's latest drivvel...

It seems almost as if Liam has moved from the realms of misrepresentation to downright fiction. The kind of descriptions coming out from this article are appalling...and therefore probably untrue.

Clinical trials simply aren't run like that - especially ones with kids - especially ones using existing therapies in an attempt simply to expand the access.

I should know - I've worked on several clinical studies with kids, some of them designed to expand access (none with HIV though).

They describe dosing schedules of midnight, 3am, 5am...these simply wouldn't exist. They're entirely impractical for post-study use. They describe changes in medications, as if ideas were being thrown around at will. You simply cannot run a study like that (literally, you will get meaningless information and the IRB won't let you!) The regulatory issues are addressed by a letter from the NY State health department here.

Liam describes a child "bleeding from every orifice" after being given thalidomide, which has actually been used to TREAT gastrointestinal bleeding and doesn't have bleeding as a side effect (except abnormal menstrual bleeding). If you're going to name-drop a well known "disaster" drug, at least have the sense to check whether it can cause the side effects you're accusing it of causing...

If a child "expressed that [they] don't want to take the drugs" they don't. You are not allowed to force someone, anyone, even someone below the age of "consent" to participate in a clinical trial. Kids get special protection under international agreements for clinical research.

I've written to the ICC, maybe I can get more information about this thing.

Confusion over PCR

2005-07-12T12:14:00.000-04:00

Confusion over PCR

It's no wonder that the dissident movement continues so long as this kind of confusion, and misinformation, continues.

The question is - if PCR copies fragments, doesn't that mean the virus is already fragmented?

Sadly this is a case of a little knowledge being a dangerous thing... PCR is MADE to copy fragments. Simply put, two small "primers" are used that are short chunks of DNA designed to match a desired sequence. One primer binds at the start of the sequence of interest, the other binds at the end of the sequence. You then start to copy DNA, and hopefully the reaction will proceed long enough so that the fragment overlaps. You then heat everything up so it all falls apart, then cool it to re-anneal the primers. Some of the "start" primers will now bind to the short sequence you amplified up from the "end" primer, and complete the double-stranded DNA. The same thing happens to the short fragment amplified up from the start primers.

After several rounds of amplification you have your original template, which may be several hundreds or thousands of bases long, several single-stranded or partially double-stranded fragments of DNA, and a large number of perfect double-stranded fragments which contain the start sequence, the end sequence, and everything in between.

As such, even if you were to start with an entire chromosome from a human, you could only PCR up a fragment. That's how it works.

The later commentators to the thread on DAG only serve up more twaddle, but talking about replicating RNA in cell culture. Frankly, that's ludicrous. RNA would be rapidly degraded in cell culture if it wasn't being made by the cells or an infection of the culture. RNA cannot replicate on its own. Also the cultures used to grow HIV are NOT frequently stimulated, in direct contradiction to what the dissidents will tell you. Some of the early culture systems were stimulated in order to activate the T cells (HIV can infect but cannot grow in non-activated T cells - the explanation is that it hijacks the same transcription factors that activated T cells use...no rocket science). As time went on, the techniques improved. I've grown HIV in long and short term cultures (anything from 10 to over 190 days) in unstimulated T cells called Jurkats. So they're lying on two counts - RNA won't be replicated in a culture, and the virus cultures don't need stimulating anyway.

In fact they're lying on three counts, by suggesting that the stimulation will result in the appearance of virus-like particles and activity. A simple thing called a control culture, performed repeatedly and published alongside much of the HIV culture literature, put the lie to that.

The other thing about PCR is that they complain that these fragments only copy fragments of the virus, not the entire genome. How do we know that these fragments ARE the virus? They're forgetting that whether you copy 100 bases or 10,000 it's irrelevant - the accuracy of the reaction depends in both instances on these primers, which are only around 20 bases long.

It all just goes to show that they really don't understand what it is they're criticising, but then if they did understand it, they wouldn't criticise it.

BMJ Shuts down AIDS dissent

2005-06-06T07:40:00.000-04:00

BMJ Policy change

For a long time now, AIDS dissidents have been using the BMJ rapid responses to tout their cause. Several have been claiming "publication" in the BMJ, despite the obvious nature of the RR's - more like that of a Bulletin Board. Myself and others wasted countless hours of our time trying to shut them down and point out their errors for the public. For the last few months at least they've been quiet, as apparently the major players got fed up and/or realised the futility of the exercise.

Now the BMJ has brought in new guidelines for Rapid Responses. Not only that, but they have specifically recognized the "AIDS deniers", meaning that despite allowing their posts to remain online, they consider them to be a flawed viewpoint.

A small victory perhaps, in a war that should never have started.

Housing Works AIDS Issues Update: GuestView: Denial Equals Death

2005-05-28T09:53:00.001-04:00

Housing Works AIDS Issues Update: GuestView: Denial Equals Death

It would be a pleasure to throw what little weight this blog has into the fray :o)

*************

Denial = Death: Defend Incarnation Children's Center and Access to HIV Treatment

For the last year and a half, a small skilled nursing facility in Washington Heights for children with AIDS called Incarnation Children's Center (ICC) has been under increasingly intense attack by HIV denialists, a dangerously deluded group of people who believe that HIV is not the cause of AIDS, and that people with HIV should not be given antiretroviral drugs. On May 5, the New York City Council General Welfare Committee held a bizarre hearing endorsing the HIV denialists' claims. It's possible that the outcome will be that children with AIDS in foster care will again be denied access to state of the art care.

HIV denialists have been around for years, annoying activists,
clinicians and service providers who regard them as crackpots whose antics shouldn't be allowed to distract us from our urgent work. We can no longer ignore them. In a world increasingly hostile to science, the lies spread by the denialists are having an effect, impeding access to HIV medication to people of color in U.S. cities and in Africa. We must respond. We must defend HIV/AIDS prevention workers and clinical and service providers like ICC. We must fight back with the truth: HIV causes AIDS. Antiretroviral treatments save lives.

The attacks on ICC began with a sensationalist story written by Liam Scheff, a self-described "AIDS dissent journalist," and circulated on the Internet. The New York Post picked up the story in March 2004, eliciting a spasm of misinformed grandstanding from a few City Council members. But the claims that children at ICC were "guinea pigs" who were being "tortured" in hideous medical experiments by a cabal of plotters including the National Institutes of Health (NIH), the Catholic Archdiocese, GlaxoSmithKline, Columbia University and the city's Administration of Children's Services (ACS) weren't taken too seriously until the BBC2 aired a version of the story in November 2004.

Regrettably, the HIV denialists have since been joined by African-American nationalists affiliated with the December 12th Movement. Their rage is directed primarily at ACS, which placed the children at ICC. They have started organizing protests outside ICC, thus outing the residents as children with AIDS. The HIV denialists have successfully worked the independent media network; over the last six months, WBAI, NYC's Pacifica radio station, and "Democracy Now!" have repeatedly and uncritically reiterated the charges against ICC.

They've been joined by the extremist right: on May 6, the Traditional Values Coalition urged U.S. attorney general and torture theorist Alberto Gonzales to launch a criminal investigation into the NIH for supporting foster children's inclusion in clinical trials, "as well as [into] anyone who looked the other way or financed these atrocities."

What is the truth? When ICC was founded in 1988, children with HIV/AIDS who were in foster care in New York City were not allowed to participate in clinical trials. As new medications were developed--including those for AIDS-defining opportunistic infections and, eventually, antiretroviral drugs--they were tested on, and approved for, adult populations first, and only then considered for children. HIV-positive children lucky enough to live with their birthparents could be enrolled in clinical trials and get the best available care. But those in the foster care system, who were overwhelmingly black and Latino, could not. These children were denied access to life-saving drugs simply because they were in foster care.

ICC and other advocates for children with HIV successfully fought to have the policy that discriminated against foster kids changed. Almost all of the children from the ICC clinical trials period, children who would otherwise have died, are alive and well today because of what ICC and other advocates for children accomplished. Those children were not "guinea pigs." They were children with a deadly infection receiving state-of-the-art medical care and life-saving drugs already proven to be effective in adults.

The denialists emphasize the sometimes serious side effects of antiretroviral medications. Are these difficult drugs to live with? Yes, but the side effects are greatly outweighed by the benefits of treatment. And the children at ICC had the advantage of living in a structured, supportive setting that ensured that they could adhere to complex regimens with stringent dietary requirements, and on-site health care that enabled rapid identification of, and response to, any side effects.

The HIV denialists say that the young children at ICC could not refuse the drugs or fight off the "researchers" who gave them their medications. Should children of three, six or even 12 years get to decide if they will or will not take their medicine? Of course not, particularly when irregular dosing may result in multiply drug-resistant HIV. All responsible parents and caregivers understand that children can't make crucial life-and-death decisions for themselves, and the law recognizes this fact too, such that children can neither give nor withhold medical consent. [1] Columbia University ran the clinical trials-the only way the kids could get the drugs that kept them alive. They were closely monitored by the loving, expert and compassionate staff of ICC, and by the National Institutes of Health and the ACS. The HIV denialists see a conspiracy where there were in fact multiple layers of supervision.

The denialists suggest that there is something evil in the cessation of the "experiments" at ICC in 2002. Why were the trials "abruptly halted?" Because, as a result of the successful treatment of children in the clinical trials, those drugs were approved as safe and effective for pediatric populations. But the denialists see even this as sinister: Now foster kids with HIV are being given anti-viral medications not just experimentally but as routine "treatment," Scheff charged on WBAI on May 10. That's true. And that's good.

Were the children at ICC stolen from their parents to be used for experiments? Absolutely not. The parents of many children at ICC had died from AIDS; others were incapacitated by illness, drugs, and homelessness and unable to care for very sick children. That's why the kids were in the foster care system. Until ICC was founded, orphaned and unparented HIV-positive kids at Harlem Hospital were stuck there as "boarder babies"; too sick for regular foster care, they had to live in the hospital. The denialists represent ACS as not merely neglectful but complicit in a "full-blown criminal conspiracy" when it placed HIV-positive kids in ICC. ACS is always (and often justifiably) an easy target. But what ACS did then was, for once, really wonderful: It put kids with HIV/AIDS who had no other home into a cozy, first-rate specialized care facility where they had access to state-of-the-art combination anti-viral therapy under the expert supervision of a brilliant and compassionate staff. That's not a scandal to be investigated; it's an incredible accomplishment to be celebrated.

Thanks to other clinical trials proving the efficacy of nevirapine in preventing perinatal transmission of HIV, and in particular to the amazing community education and care provided to pregnant women by Harlem Hospital, the incidence of perinatal HIV transmission in Washington Heights and Harlem has fallen dramatically. Almost no new HIV-infected babies are born in northern Manhattan now, and the AIDS babies of ICC are nearing adulthood.

ICC is but one example of the reach of the HIV denialists. On the same day as the City Council hearing against ICC earlier this month, South Africa's Health Minister Manto Tshabalala-Msimang sang the praises of lemon, garlic and beet root as treatments for people with HIV/AIDS and said her government would not be pressured into meeting antiretroviral treatment targets set by the U.N. The next day, the Matthias Rath Foundation, headed by a German vitamin magnate, ran full-page ads in the New York Times and International Herald Tribune claiming that antiretroviral drugs are toxic and AIDS should be treated with vitamins.

We need to turn around this tide of misinformation. The protesters outside Incarnation Children's Center are vowing "No more Tuskegee Experiments." We need to remind everyone that the essence of the Tuskegee atrocity was that poor people of color known by doctors to have a devastating, probably fatal infection were lied to and denied lifesaving medication that was available to others. That is precisely what the HIV denialists are doing in Washington Heights and in South Africa. Let's expose their lies as we continue the struggle for HIV prevention and treatment.

1. (For a well-informed and rational discussion of the complexities of treating HIV+ children and delivery and dosage issues, see Emily Bass' article in HIV-Plus at: http://www.aidsinfonyc.org/hivplus/issue5/kids/treat.html.

Jeanne Bergman is an AIDS and human rights activist and the original editor and writer of the Housing Works Weekly AIDS Issues Update (1995-98). Contact her at HIVkills@earthlink.net to get involved in fighting back against the HIV denialists.

Lying by Omission

2005-04-15T16:56:00.000-04:00

One of the most heinous crimes committed by the AIDS dissidents is that of lying by omission. I usually more generously refer to this as "cherry picking". It's not as if putting a spin on a research finding is actually that bad (after all, one must weigh up all the evidence before coming to a conclusion - if that's even possible!) but they do it so often and even in the face of clear contradiction.

For example on misc.health.aids one of the loudest dissidents by the name of Paul King quoted a paragraph from a CDC website refering to condom use. He was trying to show that condoms don't protect against HIV.

"At a Washington, D.C., news conference, the 10,000-member Physicians Consortium claimed that the CDC has known for years that condoms offer little protection against sexually transmitted diseases such as gonorrhea, chlamydia, syphilis and genital herpes.

The NIH panel concluded that there was "insufficient evidence" that condoms protect against STDs."

The REAL wording is somewhat different.

"At a Washington, D.C., news conference, the 10,000-member Physicians Consortium claimed that the CDC has known for years that while condoms are 85 percent effective in helping prevent the spread of HIV, they offer less protection against sexually transmitted diseases such as gonorrhea, chlamydia, syphilis and genital herpes.

While finding that latex condoms can be effective in preventing the spread of HIV and in protecting men from contracting gonorrhea from a female partner, the NIH panel concluded that there was "insufficient evidence" that condoms protect against other STDs."

Fox News Story

More recently, another "big" guy on the dissident scene (Chris Tyler, the moderator who stopped me educating the readers of AIDSmyth.Exposed on MSN) wrote into the BMJ listing several studies which he said supported the role of drugs in causing immune suppression.

A prospective study of male homosexuals using psychoactive and sexual stimulants demonstrated that their T-cells may decline prior to infection with 'HIV'. For example, the T-cells of 37 gay men from San Francisco declined steadily prior to HIV infection for 1.5 years from over 1200 to below 800 per µl (Lang et al., 1989).

In some case they had fewer than 500 T-cells 1.5 years before seroconversion (Lang et al., 1987).

Other studies of the same cohort of homosexual men from San Francisco described extensive use of recreational drugs including nitrites (Darrow et al., 1987; Moss, 1987; Ascher et al., 1993; Duesberg, 1993d; Ellison, Downey and Duesberg, 1995). Likewise 33 HIV-free male homosexuals from Vancouver, had "acquired" immunodeficiency prior to HIV infection (Marion et al., 1989). While this study did not mention drug use, other articles by the authors reported that all men of this cohort had used nitrites, cocaine and amphetamines (Archibald et al., 1992; Duesberg, 1993f; Schechter et al., 1993c).

In 1994, a study of IV drug users in New York (Des Jarlais et al., 1993) showed that "The relative risk for seroconversion among subjects with one or more CD4 count <500>500 cells/uL was 4.53".

A similar study in Italy (Nicolosi et al., 1990) showed that "low number of T4 cells was the highest risk factor for HIV infection", that is, decrease in T4 cells is a risk factor for seroconversion and not vice versa.

When I got around to reading the sources quoted, I got a nice surprise...

I wonder though why Mr Tyler quotes from Des Jarlais but omits the following:

"We studied CD4 cell counts and percentages from 1984 to 1992 among 1,246 HIV-seronegative injecting drug users in New York City, a population at very high risk for exposure to bloodborne pathogens. Severe CD4 lymphocytopenia was rare, and there was no evidence of an increase over time. Of 229 subjects with longitudinal data, only four met the surveillance definition for "idiopathic CD4 lymphocytopenia" (ICL)."

Hardly glowing evidence of support for the drug-AIDS hypothesis!

Marion et al don't actually demonstrate any immune deficiency at all, aside from lack of responses to DNCB (a chemical that can cause skin reactions). Responses to TB protein, candida and trichopyhton were all normal.

Lang et al actually say:

"The three groups were 37 HIV seroconverters, 304 prevalent HIV seropositives remaining free of the acquired immunodeficiency syndrome (AIDS), and 69 men who developed AIDS during observation. Six months before seroconversion, CD4 levels were similar among HIV seroconverters and 356 seronegative controls. Within 18 months of seroconversion, mean CD4 levels fell to the level of the prevalent seropositives at study entry."

I do not think these are very good arguments for the drug-AIDS hypothesis. Lang et al actually is excellent evidence for HIV infection leading to immune failure.

I recently pulled up the Nicolosi paper as well: they looked at around 460 seronegative IV drug users for an average of 10.4 months. Plenty of time to notice a loss of CD4 T cells...

The incidence rate of HIV infection was 7.4 per 100 person-years, equivalent to a one-year risk of 7.3%. Relative risk was higher in subjects who had been using intravenous drugs for less than 2 years (RR = 2.3). In a case-control analysis, recent frequent syringe sharing was the behavioral variable most strongly associated with HIV infection, with the highest risk in subjects sharing often (OR = 6.1, 90% CI = 2.6-14.7). We found no association with the use of cocaine in addition to heroin nor with sexual habits. Among biologic variables, relative risks were increased in individuals whose T4-lymphocyte count was lower than 1,000 at first visit (RR = 8.5, 90% CI = 2.9-24.3) or who were carrying HBsAg (RR = 1.9, 90% CI = 0.8-4.2).

Note that the normal range of CD4 counts is usually quoted as between 500 and 2000 with the average at around 1000. AIDS is judged to occur at a level of 200, since that is when most opportunistic infections start to become more common than background. It's no surprise that an infection (HIV) is more common in those with lower immune function (as judged by CD4 count at any rate). Only HIV infection seems to be capable of dropping CD4 counts below 200, and lower.

Remember - the opportunistic infections are merely the result of AIDS, not AIDS itself...

More viral idiocies

2005-04-15T16:34:00.000-04:00

Marburg Virus

These guys have once again amazed me with their denial and pseudoscience. The bizarrely infectious viral hemorrhagic fever of Marburg virus has sprung up in Angola, killing around 215 people (including at least 9 doctors and nurses who were treating the patients) as of my last ProMed update this morning.

These guys are blaming it on sanitation, vaccination reactions and poor food.

I very nearly posted a prediction here that they would make this kind of monumental error, but didn't honestly think they were that stupid. Apparently I was wrong. What's more frightening is the clearly unqualified people offering "expert" opinions on virology who clearly don't have a clue....not exactly the best source for your HIV/AIDS educational material.

Recent AIDS Myth Exposed Question

2005-02-28T20:59:00.000-05:00

Factor VIII

Since I can't respond to the forum as myself, I'll do so here, just in case someone might be interested.

In fact, us "mainstream guys" addressed this point quite recently (I personally replied on Jan 5th of this year). There are several things wrong with the Perth Group's assertations regarding HIV, as you might expect by now. They say:

QUOTE
In January 1994, the CDC (25) communicated the following experimental data and conclusion: "In order to obtain data on the survival of HIV, laboratory studies have required the use of artificially high concentrations of laboratory grown virus...the amount of virus studied is not found in human specimens or anyplace else in nature,...it does not spread or maintain infectiousness outside its host. Although these unnatural concentrations of HIV can be kept alive under precisely controlled and limited laboratory conditions, CDC studies have shown that drying of even these high concentrations of HIV reduces the number of infectious viruses by 90 to 99 percent within several hours.

Since the HIV concentrations used in laboratory studies are much higher than those actually found in blood or other body specimens, drying of HIV-infected human blood or other body fluids reduces the theoretical risk of environmental transmission to that which has been observed-essentially zero".

Since: (a) in most instances, if not all, the time between phlebotomy and conversion of pooled plasma to factor VIII concentrate is considerably greater than 3 hours; (b) factor VIII is made from plasma which is cell free; (c ) the late 1970s factor VIII has been supplied as a dry powder which may spend weeks or months waiting use; how can one reconcile the above facts with the view that haemophiliacs are infected with HIV via contaminated factor VIII concentrates?
END QUOTE

However, factor VIII is not made by simple drying. It's made by lyophilisation, which is a method of rapid freeze-drying that is specifically intended to preserve protein structure. One would almost expect lyophilisation to protect HIV against degradation!

In particular, there are experiments where HIV was introduced and recovered from lyophilised factor VIII [1]. Heat treatment and filtration both protect against infectious HIV, and heat-treated factor VIII is now the standard and fairly clearly protective [2].

The other point is ridiculous when faced with the work of Pantaleo, Jackson and Ho which I keep citing [3, 4, 5]. There is plenty HIV to go around - thousands of infectious units per ml - it's just not enough to get a decent EM image using peripheral blood samples. Gelderblom remember said he needed maybe 10 billion virions per ml. The idea that HIV was hard to find is a long-standing myth based purely on the fact that the very early culture techniques were inefficient. Ho et al for instance were probably detecting individual infected cells in their assay.

1. McDougal et al. J Clin Invest. 1985 Aug;76(2):875-7. "Thermal
inactivation of the acquired immunodeficiency syndrome virus, human T lymphotropic virus-III/lymphadenopathy-associated virus, with special reference to antihemophilic factor.

2. 8. Rouzioux, C., S. Chamaret, L. Montagnier, V. Carnelli, G.
Rolland, and P. M. Mannucci. 1985. Absence of antibodies to AIDS virus in haemophiliacs treated with heat-treated Factor VIII concentrate. Lancet. 1:271-272.

3. Pantaleo et al Nature. 1993 Mar 25;362(6418):355-8. "HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease."

4. Ho et al NEJM 1989 321:pp 1621-1625 "Quantitation of human
immunodeficiency virus type 1 in the blood of infected persons"

5. Jackson et al J Clinical Mole Bio 1990 pp 16-19 "Human
immunodeficiency virus type 1 detected in all seropositive symptomatic and asymptomatic individuals"

Oh the irony!

2005-02-15T10:21:00.000-05:00

One of the more eloquent and polite dissidents recently brought my attention to the following paper:

A new transmissible AIDS-like disease in mice induced by alloimmune stimuli.

Nat Med. 1997 Jan;3(1):37-41.

Ter-Grigorov VS, Krifuks O, Liubashevsky E, Nyska A, Trainin Z, Toder V.

Department of Immunology and Pathology, Kimron Veterinary Institute, Bet-Dagan, Israel.

The search for a suitable and reliable animal model for human AIDS that is easy to use on a large scale continues. Here we describe a new condition in mice that closely resembles human AIDS, namely, chronic lymphoproliferation with dramatic depletion of CD4-positive cells, progressive impairment of the immune responses, and Kaposi's sarcoma-like tumors or terminal B-lymphomas. The AIDS-like disease was primarily induced by mating BALB/c female mice to C57BL/6 males during a 1-year period (7-10 allogeneic pregnancies) followed by immunization with paternal lymphocytes. The disease is sexually and vertically transmissible, transferrable by cell-free plasma and is associated with autoimmune reactions to major histocompatibility complex antigens and CD4 cells. We hope that this becomes a model for studying the mechanisms of AIDS immunopathogenesis and immune-based treatment approaches.

He was clearly trying to show that an AIDS-like illness could be induced by something as mundane as cross-mating. I followed the paper trial however and discovered the following:

Characterization of a novel murine retrovirus mixture that facilitates hematopoiesis.

J Virol. 2002 Dec;76(23):12112-22.

Hook LM, Jude BA, Ter-Grigorov VS, Hartley JW, Morse HC 3rd, Trainin Z, Toder V, Chervonsky AV, Golovkina TV.

The Jackson Laboratory, Bar Harbor, Maine 04609, USA.

A new virus previously arose in BALB/c females mated repeatedly to C57BL/6 (B6) males and then injected with fixed, activated B6 male spleen cells (V. S. Ter-Grigorov, O. Krifuks, E. Liubashevsky, A. Nyska, Z. Trainin, and V. Toder, Nat. Med. 3:37-41, 1997). In the present study, BALB/cJ mice inoculated with virus-containing plasma from affected mice developed splenomegaly, which was caused by increased numbers of Sca-1(+) Lin(-) hematopoietic stem cells (HSC) and their differentiated progeny. Biological and molecular analyses of a new virus revealed a mixture of murine leukemia viruses (MuLVs). These MuLVs comprised ecotropic and mink lung cell focus-forming (MCF) virus classes and are termed Rauscher-like MuLVs because they bear numerous similarities to the ecotropic and MCF viruses of the Rauscher MuLV complex but do not include a spleen focus-forming virus. The ecotropic virus component alone transferred some disease characteristics, while MCF virus alone did not. Thus, we have described a novel virus mixture, termed Rauscher-like MuLV, that causes an increase in hematopoiesis due to activation of pluripotent HSC. Experiments using mice and a protocol that replicated the pregnancy and immunization strategy of the original experiment demonstrated that endogenous BALB/c mouse ecotropic and xenotropic MuLVs are activated by these treatments. Emv1 was expressed in the spleens of multiparous mice but not in those of virgin mice, and Bxv1Emv1-pseudotyped MuLVs were recovered following injection of fixed, activated B6 cells. Thus, multiple pregnancies and allostimuli appear to have provided the signals required for activation of and recombination among endogenous viruses and could have resulted in generation of the Rauscher-like MuLV mixture.

How ironic that the dissident quoted an article that shows a retrovirus can induce an AIDS-like illness :o) Basically, if something doesn't sound like it jives with the conventional view of HIV and AIDS, check the sources.

Staring them in the face

2005-02-15T09:56:00.000-05:00

This thread from a dissident discussion group is telling. One person writes:

"If they're able to strip HIV of it's disease-causing components (which sounds like quite a feat), then why the hell can't they create a vaccine?".

A moderator steps in with:

"Well of course all those 'expert scientists' didn't want to bother us with too technical details on how in the world they managed to re-engineer something that no one can seem to find in fresh, uncultured human blood."

No one there seems to be thinking the obvious: maybe they were lied to about how much HIV there is in infected people.

The design of the construct is actually presented in the published paper, available as an online article from Nature. The supplementary figure 1 has the construct map. Engineering HIV is done every day - I've constructed at least 5 unique HIV plasmids and re-engineered several old ones using the designs of previous workers. Removing the pathogenic bits is relatively easy, but then you have a major problem in that the virus effectively dies! You need supportive DNA constructs in order to make more "virus". The safer you make it, the less effective the virus becomes: and judging from the maps they ripped the guts out of HIV. Practically the only stuff left is the regulatory regions and those structures involved in packaging and efficient gene insertion. There are no antigenic regions that I can obviously see, so this kind of approach is actually the exact opposite of what you would do to create a vaccine!

As for how much HIV there is - that all depends on how much you want there to be. If you don't have a pathogenic organism, then likely you won't have the problem of the virus hiding away in the lymph nodes. Despite that, in AIDS patients Ho et al found enough virus in a single cc of blood to seed 3,500 virus cultures. Most of that was from infected cells rather than cell-free virus, but it still highlights the amount of HIV in the body.

None of this is new, or unusual, or breaks any "rules" of genetics or virology. Why it is denied by the dissidents is difficult to understand.

Dissent only for the Dissidents

2005-02-13T19:52:00.000-05:00

A few days back I tried replying to an article on a dissident webboard about cervical cancer and HPV (human papilloma virus). Someone was trying to make the case that HPV was another HIV/AIDS situation, an unsupported virus cause of an illness. I tried posting an article showing that HPV was found in 98% of cervical cancer specimens, and that was only looking for the high-risk serotypes!

They banned me. They stopped my login from even being able to view the site.

Today someone has posted a request for a virologist to explain a certain concept about HIV.

How, if the moderators actively prevent anyone with an actual education in the field from contributing to the discussion?

This is also a measure of the denial out there - that the moderators will go so far as to prevent scientific fact about unrelated illness from being made available to their readers. It seems the dissidents are being treated like mushrooms - kept in the dark and fed shit.

With friends like these...

2005-02-08T22:17:00.000-05:00

Well, so much for appreciation! This rather long-winded discussion started off reasonably enough but quickly turned nasty when I pointed out that the source (Harvey Bialy) was wrong. Bialy promptly lost it... and has started spamming my work email with vaguely insulting messages. God Bless filters :o)

The host then turned rather nasty by jumping to a whole bunch of conclusions - but I suppose what can you expect from someone who swallows the AIDS dissident crap hook-line and sinker?

The good news, I have at least now got a discussion going on with Prof Duesberg, so maybe the next post here will be more useful.

In the meantime, the third link with contributions I made to the Esmay Blog is here.

Double Standards

2004-12-28T13:02:00.000-05:00

I'm constantly amazed at the Dissident ability to have double standards. On the one hand they are perfectly happy to say that Factor VIII exists, and moreover that the methods used to isolate and characterise it are valid. On the other hand they then start spouting pseudoscience (like factor VIII is a foreign protein!!! It's human and genetically conserved!) and then that the standards of HIV genetics and proteomics are insufficient.

Bizarre.

Liam Scheff Sadly misleads

2004-12-19T22:01:00.000-05:00

Liam Scheff would do well to actually educate himself on HIV and AIDS. He was on a radio broadcast this afternoon, which I had the misfortune to turn into.

It made me physically sick to hear him.

Talking about the HIVNET 012 Ugandan study on Nevirapine, he firstly said that treating HIV transmission at the time of birth was wrong because mother and fetus have shared blood for 9 months. This is simply ludicrous, since the placenta acts as a specific barrier to PREVENT blood from mixing. HIV transmission during pregnancy is unusual, since most infections occur at the time of birth when the infant travels through the birth canal. This is why C-sections prevent infection!

He also said that pregnancy can produce false positive HIV infections, but made it sound as if every pregnancy did this, instead of the 1.6% normally quoted (and more recent studies have put it well under 1%). He stated that the maternal diagnoses in the study were made using ELISA, when in fact they used the full diagnostic test with confirmatory Western Blot. He also said that the kids were diagnosed using an unapproved RNA test, when in fact several tests are used routinely for diagnosis in neonates. The children in that particular study were in addition subject to very stringent diagnostic tests including multiple RNA tests, virus culture, and serology at 18 months of age.

All of this is stated in the study protocol which he either hasn't read or chose to ignore. I rather think he's just ignorant on the whole thing.

Sadly I wasn't in a position to listen to the whole show or phone in, but I did write. What concerns me is that laymen will have listened to this and may very well believe it. One of the hazards of free speech, especially in this situation, is that there is no personal backlash for lying.

Clinical Trial Lambasted in the UK

2004-12-18T21:30:00.000-05:00

Informed AIDS article.

This describes the latest alleged debacle regarding a clinical trial in New York city. It's been filling the Dissident press recently, along with the Nevirapine toxicity story.

The NYC episode got airtime on the BBC in England, and the article here rather neatly summarises the problems it has. Sadly they're unlikely to sway many of the Dissidents.

I thought it worth pointing out that it's no real surprise there was so much negative spin on the story if the BBC used an AIDS dissident as a "scientific" source. Be wary of what you read...

Latest BMJ rebuttal

2004-10-01T11:35:00.000-04:00

It's been a while, but this latest offering I made to the BMJ (as of now, not yet accepted) is one of my best. In it I clearly lay out the current understanding of HIV pathogenesis, as well as countering several Perth Group points from their recent post.

****************

Since my description of the mechanism of HIV-induced immunesuppression of a month ago was written "off the cuff", and the Perth Group have recently requested references, here they are.

Firstly however, it might be worth clarifying some more of the Perth Group's misconceptions.

HIV infection can be demonstrated not just by viral load (which isn't approved for primary diagnosis anyway) or combination ELISA/Western Blot criteria, but also through lymph node cultures, peripheral blood cultures, p24 antigen detection, DNA proviral detection etc. All of these have uses as investigational or clinical diagnostic criteria in certain circumstances. As I showed here previously, HIV culture correlates practically 100% with the presence or absence of HIV positive serology. [1 -3] These make a reasonable Gold Standard and surpass that of many other diagnostic criteria in infectious disease. The Perth Group have argued that without isolation by their criteria (criteria of people who do not work in the field of retrovirology) the protein and nucleotide sequences attributed to HIV cannot be said to be so. HIV has been isolated and characterised at the molecular level by criteria surpassing those of many other micro-organisms - sufficient to produce the protein, serological and nucleotide-based detection methods to the satisfaction of general science. The Perth Group have repeatedly demonstrated their ignorance of basic scientific method and fact by requesting clarification of numerous principles and facts here on the Rapid Responses, and so their opinions regarding the validity of the current HIV-detection methods are, in my eyes, largely worthless.

Secondly, it is clear that CD4 cells vary over time, but there is a profound and continuing decline seen during HIV infection that is highly unusual. The fact that CD4 T cell levels vary is precisely why single CD4 counts are not taken in isolation when making a diagnosis of presumptive HIV infection or progression to AIDS (I'm assuming that since the Perth Group are not in clinical practise with HIV patients they were unaware of this fact). What is important is that HIV can induce a decline in CD4 counts, not that all low CD4 counts are due to HIV! [4, 5] By this criteria, the Perth Group would argue that since not all anaemics have low iron, iron deficiency cannot cause anaemia. What about post-influenzal bacterial pneumonia? Does this mean that we should stop flu vaccination in the elderly because flu isn't the primary cause of death? The Perth Group point out that in the MACS study, after an AIDS-defining CD4 count of <200/ul, 10% percent of patients were "alive and well" after 6 years. Errr...that implies that 90% were not!!!! The fact that the likelihood of being well dropped with time further supports the chronic and progressive nature of AIDS, as rejected by the Perth Group. To do so in the face of contradictory evidence, to QUOTE this very evidence, is entertaining for myself but no doubt hugely misleading to the layman - it is no surprise that Perth Group publications have been rejected by the peer review process if they display the same level of logic and analysis.

Thirdly, the same caveat about low CD4 counts applies to the appearance of opportunistic infections (OIs). Transient low counts may not represent a true loss of CD4 T cells or immune function, but the fact that a low CD4 count correlates with declining immunity and increased risk of OIs cannot be argued against with any degree of honesty. [e.g 6, 7] It's not so much that all individuals with low CD4 counts should get AIDS OI's, or that all people with AIDS-OI's will have a low CD4 count. It is that individuals with a low CD4 count will have an increased RISK of getting an OI - this is indisputible. To establish a false argument based on dogmatic logic and interpretation is not a good approach to unbiased science. They seem extraordinarily hung up on KS as a measure of profound immune suppression, when the understanding among AIDS researchers is that it can appear at higher levels of immune function than other OI's. They then quote the supporting literature in apparent indignation that the wool was pulled over their eyes: when in fact it's merely that they misunderstood KS in the first place. It is perhaps the fact that KS can appear earlier than other OIs that makes it several tens of thousands of times more common in HIV+ patients than the normal population (as I have shown here previously). It is obvious that someone in a plastic bubble will be unlikely to get an OI - it is a simple extrapolation to state that someone in the developed world is less likely to get TB than someone in the developing world, or that a homosexual HIV+ person is more likely to have KS (through sexually acquired HHV8 infection) than a HIV+ haemophiliac. Exposures will dictate which OIs occur to a large degree, and where there is no exposure to a particular pathogen, no OI will occur! To argue that decreased CD4 cell number does not influence OI's and then present a series of HIV-related pulmonary infections of which 116 of 134 cases (86.5%) had CD4 counts lower than 200 (only 20% of the average level in uninfected controls) is hilarious. To use a group of ITU patients as a comparison with "only" 17% having a CD4 count below 200 is laughable - the mere act of being on an ITU, and presumably intubated and/or comatose, puts patients at risk of pneumonia in the absence of anything else. This displays a shocking lack of appreciation of the limits of modern interventional medicine.

Fourthly, sexual infections may well be bi-directionally transmitted, but there is no reason to suppose that to be exclusively true. At the very least it is not hard to entertain the idea that perhaps transmission in one direction would be far more efficient than the other. Most obviously, infection due to a viral innoculum supplied by semen would be far more likely to occur in the receptive rather than the insertive partner! STDs where this is not the case (e.g. herpes, crabs) would be expected to have a far more equal distribution between the partners. Additionally, insertive intercourse is not completely without risk, merely at a low level of risk. [8] The fact that in the MACS study continuing receptive anal intercourse was an independant predictor of progression within HIV+ men, suggests that dual-infection may be a reason for faster progression, as noted in several anecdotal reports and supported by some work from Kenya in prostitutes [9]. It's entertaining to read the Perth Group quote a paper that says:"sexually transmitted co-factors, pre- seroconversion and/or postseroconversion…augment (or determine) the rate of progression to AIDS" and conclude that "co-factors that augment (or determine)" progression to AIDS are non-infectious". The "sexually transmitted" bit somewhat implies an infectious cause, but then coming to opposite conclusions to the original authors of an article is what the Perth Group do best. No doubt their dogmatic approach to epidemiology (among other sciences) is hindering their cognitive ability, since their assumptions about sexually transmitted infections are wrong, as stated above. I'm actually surprised they quote this study, since it also shows that aside from anything else, AIDS only occurs in those who are seropositive to HIV!

Fifthly, the transient loss of CD4 cells seen during primary infection is proof-positive that HIV induces CD4 cell loss! The fact that the cases of PCP reported all had counts lower than 100 (62-91/ ul - literally decimated compared to the normal range) also shows the link between CD4 cell count and immune function! The fact that the Perth Group interpret these results otherwise is crazy. The transient dip seen post infection is well documented (see ref 4 for graphs) and as such the return to normal, or near normal, would be expected. This in fact supports one of my points below about immune responses to HIV controlling primary infection [17]! They state that the CD4 counts were normal prior to PCP, but since this was also prior to HIV infection (by at least 1 to 2 months) it is a ridiculous argument to say that "[Preceding CD4 decline]...is not the case even for...PCP". Once again their own references (their own abstracts no less!) refute their statements. They have formed an argument that can be summarised as: (transient, tiny, brief) dips in CD4 count occur in uninfected people, and these are not associated with OIs: the (profound, prolonged, progressive) low CD4 counts associated with HIV infection are associated with OIs, but cannot be anything to do with low CD4 count due to the situations in uninfected controls. Mind-boggling.

Sixthly, as I pointed out in my reply to the Perth Group's original post on "OTK3...", one of the very papers they were quoting from also stated that HAART reduced the incidence of OIs, a fact supported by many longitudinal cohort studies. OI's may continue to appear, but do the Perth Group seriously expect every instance to be prevented? The fact that the Perth Group fail to accept this point of information suggests a dogmatic adherence to their beliefs that overrides any amount of logic or fact. To repeat a previously refuted statement without even a nod to the rebuttal is extremely cheeky, but par for the course here it seems.

Seventhly, if HIV antibodies are so useless, and co-factors so important, why do cohort members in a prospective, untreated population only develop AIDS or declines in CD4 T cells if they (and only after) they seroconvert...? [10-13] Why do only 5% of HIV+ people exhibit true long term non-progression whereas the vast majority show a steady decline in CD4 count? [4] No amount of armchair pseudoscience, handwaving or misrepresentation is going to detract from that.

If I didn't know better I would say that the Perth Group are actually being impersonated by someone out to discredit them...such is the level their posts have dropped to. Having removed the chaff it appears there wasn't any wheat there after all.

But to cut to the chase, here is a repost of my "mechanism" with accompanying references. Enjoy.

**************

HIV infection - > immediate CD4 cell loss through:

Trafficking to Lymph nodes [14] (activated T cells traffic)

Cell death [15, 16] (HIV is cytotoxic to T cells, in vitro at least - in vivo data less convincing)

Immune responses then become established [17]:

Cell death due to HIV decreases, immune activation decreases (T cell levels return to more normal levels [4]).

Chronic "latent" asymptomatic phase:

Ongoing immune activation keeps cells over activated and therefore replicating and trafficked towards lymph nodes. [18]

HIV preferentially infects and replicates in activated T cells [19- 21]. The biological situation is therefore supportive of continued HIV replication, assisted by the fact that it is an integrated provirus in many cells and therefore resistant to immune and drug attack [22-24]. Later activation of the proviral reservoir through antigen recognition (HIV or new infection) leads to HIV activation and cell death [21, 26]. Therefore HIV SELECTS for those cells responding to itself or new infections (a very effective immune-deficiency causing process).

Cell signalling is altered as cell cycle arrest is mediated by HIV [25], and progression through the cell cycle is required for successful cytokine production [27].

Lack of correct cytokine environment reduces T cell replacement from the thymus (hypothetical at the moment, observational evidence only, based on [18, 25, 27] and others with more clinical application: eg [28, 29]).

CD8 killer T cells preferentially destroy HIV-infected CD4 T cells, but this seems to correlate with improved outcomes due to overall control of the replication [30]. The actual anti-HIV activity may be impaired due to effects of HIV itself through CD4 T cell dysfunction [31].

All the above leads to: selective loss of activated (useful) T cells [4], cytokine skewing through chronic activation [34, 35], premature immune system aging [32] (seen in other viral infections), gradual decline in immune repertoire [33] and eventual thymic exhaustion [28, 29].

As the available T cell repertoire is reduced to the point where HIV can no longer be controlled, the infection becomes overwhelming. It is at this stage that AIDS usually occurs. [4]

I could go on, and on, and on - but this is rather more than the tip of the iceberg. I hope it (and the accompanying references, and the references within them) made for interesting reading.

***************************** Refs

1. Jackson et al J Clinical Mole Bio 1988 pp1418-1418 "Rapid and sensitive viral culture method for human immunodeficiency virus type 1."

2. Jackson et al J Clinical Mole Bio 1990 pp 16-19 "Human immunodeficiency virus type 1 detected in all seropositive symptomatic and asymptomatic individuals."

3. Ho et al NEJM 1989 321:pp 1621-1625 "Quantitation of human immunodeficiency virus type 1 in the blood of infected persons."

4. Fauci et al. Ann Intern Med. 1996 Apr 1;124(7):654-63. "Immunopathogenic mechanisms of HIV infection."

5. Munoz et al. J Acquir Immune Defic Syndr. 1988;1(4):396-404. "Predictors of decline in CD4 lymphocytes in a cohort of homosexual men infected with human immunodeficiency virus."

6. Masur et al. "CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection." Ann Intern Med. 1989 Aug 1;111(3):223-31.

7. Goedert et al. JAMA. 1987 Jan 16;257(3):331-4. "Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus.

8. Vittinghoff et al. Am J Epidemiol 1999 Aug 1;150(3):306-11 "Per- contact risk of human immunodeficiency virus transmission between male sexual partners."

9. Sarah Rowland Jones. Personal Communication based on Kaul et al. J Immunol. 2000 Feb 1;164(3):1602-11. "HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi." and earlier work.

10. Goedert et al. Science. 1986 Feb 28;231(4741):992-5. "Three-year incidence of AIDS in five cohorts of HTLV-III-infected risk group members."

11. Jaffe et al. Ann Intern Med. 1985 Aug;103(2):210-4. "The acquired immunodeficiency syndrome in a cohort of homosexual men. A six- year follow-up study."

12. Goedert et al. Eur J Epidemiol. 1985 Sep;1(3):155-9. "Epidemiological evidence that HTLV-III is the AIDS agent."

13. Goedert et al. N Engl J Med. 1989 Oct 26;321(17):1141-8. "A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia."

14. Zaunders et al. J Infect Dis. 2001 Mar 1;183(5):736-43. Epub 2001 Feb 01. "Increased turnover of CCR5+ and redistribution of CCR5- CD4 T lymphocytes during primary human immunodeficiency virus type 1 infection."

15. Gallo et al. Science. 1984 May 4;224(4648):500-3. "Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS."

16. Connor et al. J Virol. 1993 Apr;67(4):1772-7. "Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1- infected individuals."

17. Graziosi et al. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6405-9. "Kinetics of human immunodeficiency virus type 1 (HIV- 1) DNA and RNA synthesis during primary HIV-1 infection."

18. Mohri et al J Exp Med. 2001 Nov 5;194(9):1277-87. "Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy."

19. Hufert et al AIDS. 1997 Jun;11(7):849-57. "Germinal centre CD4+ T cells are an important site of HIV replication in vivo."

20. Lyerly et al AIDS Res Hum Retroviruses. 1987 Spring;3(1):87-94. "Transmission of HIV by antigen presenting cells during T-cell activation: prevention by 3'-azido-3'-deoxythymidine."

21. Margolick et al J Immunol. 1987 Mar 15;138(6):1719-23. "Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses."

22. Chun et al. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. "Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy."

23. Chun et al. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8869-73. "Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection."

24. Chun et al. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):10958- 61. "Latent reservoirs of HIV: obstacles to the eradication of virus."

25. Rogel et al. J. Virol., Feb 1995, 882-888, Vol 69, No. 2 "The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection."

26. Tobiume et al. J Gen Virol. 1998 Jun;79 ( Pt 6):1363-71. "Dependence on host cell cycle for activation of human immunodeficiency virus type 1 gene expression from latency."

27. Bird et al. Immunity. 1998 Aug;9(2):229-37. "Helper T cell differentiation is controlled by the cell cycle."

28. Ruiz-Mateos et al. Clin Exp Immunol. 2004 Jun;136(3):501-6. "Thymic volume is associated independently with the magnitude of short- and long-term repopulation of CD4+ T cells in HIV-infected adults after highly active antiretroviral therapy (HAART)."

29. de la Rosa et al. Antivir Ther. 2002 Sep;7(3):159-63. "Baseline thymic volume is a predictor for CD4 T cell repopulation in adult HIV- infected patients under highly active antiretroviral therapy."

30. Ogg et al. J Virol. 1999 Nov;73(11):9153-60. "Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression."

31. Appay et al. J Exp Med. 2000 Jul 3;192(1):63-75. "HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function."

32. Weekes et al Immunology. 1999 Nov;98(3):443-9. "Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population."

33. Pahwa et al. AIDS Res Hum Retroviruses. 2003 Jun;19(6):487-95. "CD4+ and CD8+ T cell receptor repertoire perturbations with normal levels of T cell receptor excision circles in HIV-infected, therapy-naive adolescents."

34. Spellberg and Edwards Clin Infect Dis. 2001 Jan;32(1):76-102. Epub 2000 Dec 15. "Type 1/Type 2 immunity in infectious diseases."

35. Nunnari et al. Ann Intern Med. 2003 Jul 1;139(1):26-30. "Slower progression of HIV-1 infection in persons with GB virus C co-infection correlates with an intact T-helper 1 cytokine profile."

Why Viral Loads are Useful, Relevant and Important.

2004-08-14T23:35:00.000-04:00

A commonly spread myth is that the HIV viral load tests are meaningless, non-specific and arbitrary. This myth is spread based on several lines of logic that are either flawed, misleading, or just downright lies.

Firstly a bit of background as to what a viral load test is. Simply put, a viral load is a measure of the amount of genetic material in the bloodstream, as judged by the relative amount of certain RNA molecules. In the context of HIV, viral load is used as a confirmatory test of infection, but more usually as a judge of how rapidly the disease is progressing. The higher the viral load, the faster the infection is likely to progress to AIDS, and ultimately death. The aim of anti-retroviral therapy is to reduce the viral load to below detection (less than 50 copies per ml with many modern tests).

The Dissidents do not like the test for several reasons, as discussed below.

1: “The VL test doesn’t look for actual virus, it only looks for RNA”.

This is true, but a molecular biologist would simply say “So what?” There is nothing wrong with this, no matter how many dissidents say there is or how loudly they say it. Ultimately unless you physically purify HIV from peripheral blood (see the email from Gelderblom as to why that isn’t likely with HIV) and look at it under EM, you are limited to using secondary detection measures. These will include looking for viral proteins or genetic material, or virus culture. It is a standard procedure for a great many other viruses, and increasingly for some bacteria. This argument is a bit like saying “There’s no proof I was at the scene of the crime, they’re just my fingerprints”.

2: “The VL is amplified many times then a number is back-calculated”

This isn’t really true. It is mind-numbingly obvious though that amplification HAS to be done. In order to visualize the RNA on a standard lab gel you would need to bleed 20 AIDS patients completely to get enough virus to barely see the RNA from all the virus in their bloodstreams (6.5ng). About 200 patients to make it believable at 65ng (a nanogram is a billionth of a gram) – there simply isn’t enough material. The “back calculation argument” though is very misleading. Due to the variability in this kind of amplification (called PCR – polymerase chain reaction) you must have some kind of controls. Typically these are internal controls, whereby samples of known copy-number are run at the same time in the same conditions. Then a graph can be drawn of all the “standards” and the experimental sample is then fitted to the graph. It is a common Dissident tactic to either purposefully (or through ignorance) leave out the fact that the proper controls are always done. It would be impossible to directly count the RNA strands after the amplification process has been done, which is what dissidents imply needs to be (and is) done. Instead, standard molecular techniques are used (where for example the concentration of RNA is shown by how absorbent the sample is for a certain color of light, compared to a control sample).

3. “You only look for a small part of the virus, not the entire genome”

This is true, but again the answer has to be “So what?” The big concern is that if you look at too small a sequence you might by accident discover an RNA molecule that looked similar to HIV in that small sequence. The HIV genome is about 10,000 bases long, and the viral load detects bands that are only a few hundred bases long. In order to get enough RNA to detect (actually DNA, since they copy the original RNA into DNA first because it’s far, far easier to copy and work with) many rounds of amplification have to be performed, around 20. Copying the entire 10,000 base genome would take around 20 minutes to perform per cycle, this means that with the rest of the protocol the entire process would take about 10 hours to complete! While not impossible, by limiting the process to only a few hundred bases it can be complete in an afternoon. However, by arguing that longer stretches need to be used the Dissidents only highlight their ignorance of a vital step in PCR – no matter how long your sequence is, the actual copying process is started by short stretches of DNA called oligos, which are typically 20 or so bases in length,

As such, it makes no difference whether you copy 100 or 10,000 bases, you’re going to have the same degree of accuracy, since the limiting step is the uniqueness of the oligos!

As for the specificity of the oligos, you can get a measure of how specific they are by how long they are. The chances of a single base matching are 1 in 4, since there are 4 different bases in RNA and DNA (A, C, G and T/U). The odds of two consecutive bases matching are 1 in 16. By the time you get to 20 bases you have a 1 in 1,099,511,627,776 chance of matching, or over 350 times more DNA than is in the entire human genome! Obviously certain sequences will be “conserved”, meaning their sequence is more likely to occur than pure chance would suggest. However, despite the existence of retrovirus-like sequences in the human genome (called endogenous retroviruses, HERVs), this is still very unlikely if you pick the right place to look. If you couple that with the fact that you are expecting a product of a certain size (say, 300 bases) you can be fairly sure that no other sequence of DNA, no matter how long, is going to bind to the oligos you use to produce a product of that size.

It is true that the virus RNA is only 1% of the RNA produced by an infected cell. By virus standards though, that it pretty high! That means you really only have to secure uniqueness to 99% of the RNA (if the ratio was the same as the length of genomes, you would need to show uniqueness to a 3 million-fold excess! It is exceedingly unlikely that any RNA detected would be from non-HIV sequences, and any that are would be very low levels. Normally RNA is not found outside the cell in appreciable numbers, whereas of course virus particles are definitely outside the cell! This further increases the likelihood of distinguishing HIV from any other sequence.

4. “The RNA doesn’t equate to numbers of infectious virus”

This is true, and contrary to what the Dissidents say is not assumed to be such by the scientists (an example of them putting words into our mouths). It is well recognized that 1 infectious virus equates to about 60,000 viral genomes per ml. It doesn’t matter, since we’re not trying to say that the virus in the bloodstream is causing AIDS. What?! I hear you cry, surely that’s what they say? No, that’s only what the Dissidents say the scientists say, another example of putting words into our mouths. Viral load is used as a marker because of very good reasons (detailed below) which do NOT include the assumption that the viral load is causing AIDS. In fact, it is very well recognized that the virus in the bloodstream is only a tiny portion of the virus in the body. The vast majority is to be found in lymph nodes, which is where AIDS really happens. Obviously a blood test is far easier than taking a lymph node biopsy, hence the reason why VL measurements are used instead of LN biopsies.

But how much more virus is there in lymph nodes? Far, far more than is in the bloodstream. Maybe 1 in 40 CD4 T cells in the bloodstream contain HIV in end-stage AIDS, far fewer in earlier stages of infection. In the lymph nodes maybe 1 in 4 T cells is infected! Since only 10% of T cells are in the bloodstream, it’s clear that only a small part of the virus replication goes on in the bloodstream. There are plenty of reports suggesting that LN biopsies are used as measurements of disease progression, at least there were in the days before viral load measurements!

On the other hand, it’s obvious that the relative amount of infectious RNA must equate to the viral load. Even with 1 in 60,000 being infectious, if a viral load increases 10-fold then the number of infectious virus must increase 10-fold. A small proportion does NOT equate to NO infectious virus! Having a low infectivity isn’t unusual for viruses (herpes is about 1 in 100), but HIV is admittedly worse than many. However, implying that every copy of the genome should be infectious isn’t right. This point also destroys another Dissident argument: that HIV cannot be found in infected people. Clearly if a ratio of 1 in 60,000 can be measured, is MUST be true that HIV can be cultured from patients! In fact, HIV can be cultured from all AIDS patients, and not from people without HIV antibodies.

In any case, it is known that non-infectious HIV can cause disease! The proteins contained in and on the virus have been shown to cause immunosuppression and cell dysfunction, as detailed in my refutation of Duesberg’s work.

5. “The Viral load is based on detecting RNA that hasn’t even been shown to be that of HIV”

This is blatantly false. Contrary to whatever people like the Perth Group say, HIV has been purified enough to know that the RNA molecule labeled as “HIV” is in fact that of a virus particle. The RNA encodes proteins that co-purify with it (and not cellular proteins), which to any virologist is practically 100% proof that it belongs to a virus. The fact that the Perth Group are not virologists is the only reason why they say the things they do. They quite simply have no idea what they are talking about.

6. “Anti-HIV medications reduce viral load by reducing levels of cellular RNA”

This is ludicrous. Viral loads can be reduced 100,000 fold by antiviral therapy. If cellular functions were reduced by that level you would die in very short order! Any “escapes” from therapy are correlated with mutations in the HIV proteins and RNA. This should not be happening if the effects were non-specific. Contrary to what the Dissidents say, the meds are very specific indeed. 100 to 10,000 more drug is needed to affect cells compared to virus, and that’s with the most toxic medications. The protease inhibitors can not affect cellular RNA or DNA production at all!

7. “False positive results are common”

There are several documented false-positive viral load cases. Some have led to mis-diagnoses. However, they are not as common as is suggested. Viral load is often mentioned in the same breath as p24 antigen testing, which is very clearly a bad test for diagnosis or monitoring of HIV infection. Even with the fact that viral load is a far better test, it is not used for routine diagnosis of infection. It is usually used for judgment of treatment initiation or change, as discussed below. How do these false positive results occur? The simplest explanation is that of accidentally binding to a close match of DNA in the reaction, or contamination in the lab. Due to the sensitivity of the test, detecting contamination is entirely possible. False-positives are usually low levels, around 1000 counts.

8. “HIV DNA detection is very non-specific, why should RNA be any different?”

HIV DNA detection can be non-specific, depending on the oligos used. Some cross-reaction with the endogenous viruses can occur. However, they do not produce RNA or virus particles, since they are usually inactive, so by removing the DNA and using only extra-cellular virus particles you reduce the likelihood of detecting these endogenous particles. I have seen it written that the sequences looked for: Gag and Env are “specific to HIV”. No-one with any experience with virology at all would say that: Gag and Env are simply names for genes that encode the structural proteins of a retrovirus. Every retrovirus in existence has its own version of Gag and Env: it is not surprising that depending on how you look you can confuse HIV Gag and HERV-K Gag, for example.

9. “Viral load improvements with therapy are only due to placebo effect”

Placebo means “it pleases me”. It is a psychological phenomenon. It cannot explain molecular measurements like viral load, unless they were measuring some kind of stress hormone. It also doesn’t explain why people with naturally low viral loads have strong anti-HIV immune responses, and why rising viral loads match with mutations that either escape the drugs or the immune response.

10. Viral load levels predict disease progression. This is the biggest anti-Dissident point of them all. In many studies, it is clear that the best predictor of how soon someone will progress to AIDS is how high their viral load is. This fact makes the level of viral load very important, even if it weren’t measuring infectious virus, or even HIV at all! This is undeniable. A viral load of over 30,000 equates to a 50% risk of progression to AIDS in 2 years, independent of CD4 count. Lowering viral load does correlate with reduced mortality and opportunistic infections. Lack of control of viral RNA correlates with worse outcomes. What more is there to say…?

Purifying HIV

2004-08-12T21:51:00.000-04:00

Not too long ago I got in touch with Hanz Gelderblom, a renouned electron microscopist. The Perth Group have tried to use some of his review articles to state that HIV should be visible under EM of plasma samples. Since no such EM has been published, therefore HIV cannot exist (a ludicrous statement however you look at it). Hanz however has more specific things to say...

(Paraphrased at his request from the email)

***
Despite being successful at getting EMs of HIV from cultures, in parallel experiments using plasma samples he could not get enough virus. This was because they only recieved two samples of less than 0.5ml of blood from late-stage patients, when ideally it should have been far more from the seroconversion stage when virus titre is higher. He also attempted to get virus from Africa but couldn't get samples. Collaborations with groups from Sweden and Italy also failed because no samples of sufficient titres could be obtained. From experience, he thinks he could have been successful with particle concentrations of 10^10 per ml, about 10,000 times higher than what we here [at the BMJ Rapid responses] thought would suffice. Having tried for some time on this path, he gave up attempting to isolate HIV from blood about 10 years ago.

There are several logistical problems associated with EM of HIV from blood samples as well. The best way to ensure particle stability "in the field" is to fix the sample in higher then 0.5% Glutaraldehyde (GA), to prevent shedding of gp120 knobs. However, this level of GA prevents immunolabelling which he wanted to do to characterise virally-incorporated cellular MHC molecules, but could also be used to label virion proteins. As such there is almost a mutually exclusive situation where you can either keep the virus intact, or analyse it using immunoEM. He did attempt to look at virus from pelleted samples (rather than the 2-drop method mentioned in the previously quoted article) which would have massively concentrated the sample, but even this failed due to low titres of virus (see my earlier postings for calculations of virus needed to fill a 1mm cube).

He also is of the opinion (and a highly experienced opinion it must be) that any attempts to purify or enrich HIV from plasma will induce artifacts, such as changes in virion fine structure, shedding of gp120, osmotic damage etc. Obtaining particles with HIV morphology might therefore be a practical impossibility (much like trying to observe the position and speed of a subatomic particle simultaneously).

He does however admit that maybe plasma-derived HIV is more stable than that of cell-culture derived HIV, and gives the example of Avian Leukosis Virus as a comparison. We simply do not know, because no-one has been able to do it. He feels that direct isolation of HIV from blood samples might well be possible to do, and should be done since it would give a more realistic research material to study (not, notice, in order to prove its existence!).

I am deeply grateful for Dr Gelderblom for taking the time to write
to me, and for giving me permission to quote him online.

***

Calculations performed regarding the size of HIV particles:

4/3*pi*r^3 for a 120nm diameter particle, into a 1mm cube gives a little over 1 trillion particles. Average blood volume taken to be 5 liters.

The size of the particle is such that 200 AIDS patients with viral loads of 1 million per ml would need to have their entire circulating blood volume concentrated to produce enough virus to fill a 1mm cube (a grain of salt). Viruses are small, even if they can be prolific. The total RNA purified from that (bearing in mind that each virus contains 2 copies of the genome) is about 65 nanograms, or only just enough to visualise on a standard ethidium gel. Asking for an EM from a virus that hasn't been cultured or RNA from a virus that hasn't been amplified by PCR (or culture) is simply setting up a straw-man argument.

Woohoo!

2004-08-12T21:27:00.000-04:00

My first dissident arrives! Welcome, and stay silent. It's interesting to get the attention.

As soon as I organise some more ideas I'll get another refutation up, but for now I'll just enjoy having just a little bit of power over my tiny portion of the Web :o)

Anti-Dissident Site

2004-08-11T23:03:00.000-04:00

I was recently put in touch with a vocal anti-Dissident, which is a refreshing change. All too often I find that the scientists are too quiet and those who don't know what they're talking about are too loud...

Check out DaveyBoy's link above or in the Links section (he was kind enough to link back here!). He's done some impressive work pulling a lot of sites together so deserves more than a little recognition. While not a scientist he has first-hand experience of HIV and is certainly aware of the problems that Dissidents can cause, most relevant being their ongoing attacks on orthodox support groups and information forums. How heinous can you get...

A refutation to some of Duesberg's Stuff

2004-08-09T20:18:00.000-04:00

Prof Peter Duesberg is a retrovirologist who did some of the best work on Rous Sarcoma Virus. He mapped the src oncogene, a piece of work that was incredible considering the lack of molecular techniques available at the time.

However, he applies his understanding of simple retroviruses to HIV, a complex retrovirus (complex because it contains accessory genes) and concludes that HIV cannot cause AIDS. Moreover, he goes onto say that drug use causes AIDS.

Here is my personel rebuttal to Duesberg's anti-HIV argument.

Pharmac. & Ther. Vol. 55: 201-277, 1992
AIDS ACQUIRED BY DRUG CONSUMPTION AND OTHER NONCONTAGIOUS RISK FACTORS
PETER H. DUESBERG

3. Discrepancies Between AIDS and Infectious Disease

3.1.Criteria of Infectious and Noninfectious Disease

Based on common characteristics of all orthodox infectious diseases, infectious AIDS would be predicted to:

(1) Spread randomly between the sexes. This is just as true for venereal as for other infectious diseases (Judson et al., 1980; Haverkos, 1990).

******

Except a new infectious agent that spread into the Western world (which, lets face it, is all Duesberg is talking about) through the homosexual population. Spread to women and heterosexual men would be expected (and was observed) to be slow and incomplete.

HIV spread is equal among the sexes in the heterosexual epidemic in Africa.

******

(2) Cause primary disease within weeks or months after infection, because infectious agents multiply exponentially in susceptible hosts until stopped by immunity. They are self-replicating, and thus fast acting toxins. (Although "slow" viruses are thought to be pathogenic long after neutralization by antiviral immunity (Evans, 1989c), slow pathogenicity by a neutralized virus has never been experimentally proven (Section 6.1).)

******
HIV causes an acute seroconversion illness in about 50% of those it infects. This is like most other viral illnesses, since the symptoms are not caused by the virus but instead by the release of cytokines such as IL-2 and the Interferons, which produce constitutional unwellness.

Also he is assuming that the presence of antibodies to HIV means that they are _neutralising_ antibodies, and yet he makes no effort to prove this. The fact that HIV can be detected even after an antibody response might argue against this, but doesn't take into account direct cell-to-cell spread. Many viruses persist despite antibody recognition, and antibodies do not have to be neutralising, some are in fact pathogenic. (Mitler and Hoffmann: Science 1989) Examples are HSV, EBV, VZV, Hep B. The herpes family maintain their genome in host cells, and their latency is less well understood than that of HIV. At least we know that T cell activation results in HIV expression (the same transcription factors, such as NF Kappa B are used) while for the herpes viruses we don't even have that handle. Hep B is a reversivirus, related to the retroviruses by its use of reverse transcriptase. It doesn't integate into the genome. However, it's persistance is also a mystery - there is a vigourous immune response, which results in the liver destruction which gives this virus its name (the virus is not in fact cytotoxic to liver cells). It also produces massive quantities of non-infectious particles, so much so that the viral particles have a special name (Dane particles) to distinguish them from the rest of the junk found in the serum. These may act as decoys for the virus against the immune response (ref for most of the above: Fields Virology, or any other virology textbook - Duesberg should have known all this).

Also, it is known that CD4 counts plummet during this acute stage, from ~1000 to ~500 (the lower end of normal) before picking up again as HIV-specifc immunity appears (Pantaleo et al: NEJM 1993 review). While these levels are not going to result in opportunistic infections appearing, they are a definite sign of things to come.

*******

(3) Coincide with a common, active and abundant microbe in all cases of the same disease. (Inactive microbes or microbes at low concentrations are harmless passengers, e.g. lysogenic bacteriophages, endogenous and latent retroviruses (Weiss et al., 1985), latent herpes virus or latent ubiquitous Pneumocystis and Candida infections (Freeman, 1979; Pifer, 1984; Williford Pifer et al., 1988). Hibernation is a proven microbial strategy of survival, which allows indefinite coexistence with the host without pathogenicity.)

********

There is evidence of HIV virus particles in 100% of AIDS cases and over 99% of those with anti-HIV antibodies (Jackson et al: J Clinical Molecular Biology 1988 and 1990). The low level of HIV in the plasma of infected people (often to uncultureable, though not undetectable levels) after the first week/fortnight (Piatak: Science 1993, Pantaleo et al: NEJM 1993 review) suggests that the immune system is actively hindering HIV replication, especially since antibody titres to HIV go up reciprocally. As for abundant microbe - tetanus toxin from clostridium tetani bacteria can and does kill in quantities too low to mount an immune response to. This also feeds into the following claim...

*******

(4) Coincides with a microbe that lyses or renders nonfunctional more cells than the host can spare or regenerate.

*******
And/Or hinders the regeneration of those cells. HIV reduces the CD4 cell survival time and hinders replacement from the thymus. The effect of HIV is reversed by antiviral therapies. (Duoek el al: Nature 1998, Hellerstein et al Nature 1999) HIV is cytotoxic (Yelle et al: Archives of Virology 1994, Rasheed et al: Virology 1996, ), and may be immunosuppressive even in the absence of active infection (Diamond et al: J immunology 1988, Weinhold et a l: J immunology 1989, Daniel et al: Clinical Experimental Immunology 1993, Liegler and Stites: J AIDS 1994, Theodore et al: J AIDS 1994, Schols and De Clercq: J Virol 1996, etc - I haven't even started on the accessory proteins of HIV). The immune response to the virus will, of course, attack the immune system itself. As such the number of cells the virus actually kills by infection need not be the limit of the immune dysregulation. Direct in vivo evidence of this lack of correlation between cytotoxicity and immune suppression exists in chimps (Wantanabe et al: J Virology 1991).

******

(5) Generate a predictable pattern of symptoms.

*******

Longitudinal studies shown that after ~15 years 90% of those with HIV infection with progress to a stage of gradual immune decline, with increased risk of opportunistic infections, a specific supression of cytotoxic immune responses with (usually) a simutaneous rise in antibodies.

********

Duesberg also moans that HIV cannot possibly be neurotoxic and a cause of AIDS dementia, since the retroviruses he worked on didn't infect non-dividing cells. He seems to ignore the fact that HIV does infect the non-dividing T cells, an ability later ascribed to the vpr protein found
in HIV, but not in the simple defective retroviruses he worked on. He also doesn't know that HIV's neurotoxicity is due to infection of the CD4+ astrocytes in the brain, and subsequent loss of neuronal support leading to cell death. Again - a non-direct method of disease.

There is plenty more of course, but based on this logic the argument that HIV cannot be the cause of AIDS seems untenable to me.

AZT, not toxic enough

2004-08-09T15:09:00.000-04:00

One very key part of the AIDS dissent is concerning the antiretroviral drugs. In particular, due to an early series of papers by Prof Peter Duesberg, AZT (Azidothymidine) has been targetted. It is said to be an anti-cancer drug that was canned due to being too toxic. This is false for lots of reasons.

The original inventor of AZT, Dr Richard Beltz, is quoted as saying that AZT was in fact inactive against cancer cells in the lab and in mice. This quote comes from an email to an AIDS dissident (see link) - what better source can you imagine?

"It proved to be completely inactive in all of the test systems [Dr Sartorelli] employed. In my laboratory I found AZT incapable of inhibiting the growth of Jensen sarcoma cells in vitro at very high concentrations. Thus, AZT showed no activity as a potential anticancer drug at that time."

As regards various quotes that have Dr Beltz saying that "AZT was shelved for two reasons: My studies showed that it caused cancer at any dose and it was too toxic even for short term use":

"Now let me say that I am aware of the existence of certain quotes attributed to me on the Internet, such as the one you mentioned in your letter. Such quotes are completely untrue!"

Duesberg also makes an assumption that AZT was stopped due to toxicity. From his book "Inventing the AIDS virus".

"However, when he tested the compound on cancer ridden mice, it failed to cure the cancer. Horowitz was so disappointed he never bothered publishing the experiment and eventually abandoned that line of research. The drug MUST HAVE killed the tumors, which contain dividing cells, but it so effectively destroyed healthy growing tissues that the mice died of the extreme toxicity." [Emphasis my own]

Duesberg also says that even with enzyme specificity there is so little viral DNA compared to human DNA that it must kill many more healthy cells than virally-infected cells. The evidence doesn't bear this out, with up to 100-10,000 times more drug needed to kill cells compared to virus. [refs 1-4 below]

Some have said that AZT is currently used in cancer therapy. A drug that has the same abbreviation, Azathioprine is used in treating leukaemias, but it is not Azidothymidine.

All in all, far from being a toxic anti-cancer drug that was abandoned due to toxic effects, it doesn't kill enough cells. It is, unarguably, a nasty drug. Many (perhaps a quarter to a third) of patients require blood transfusions while on it, at least they did on the older doses which were twice those of today. However, it is quite clearly not, and never was, an anti-cancer drug.

Refs:
(1) J Virol 2002, 76(12):5966-73

(2) J Biol Chem 1989, 264:6127-33

(3) Antimicrobial Agents and Chemotherapy 1990, 34:637-641

(4) NEJM 1987, 317:192-197

First Post!

2004-08-09T02:49:00.000-04:00

How original, title wise, but what the hey.

Since 1998 I've been involved with discussing the HIV/AIDS debate, that is the actual debate over whether or not HIV causes AIDS. Believe it or not, such a debate has existed in various forms since 1983.

From what I've seen, aside from conventional websites, nearly nothing has been done to directly address the various arguments used by the AIDS Dissidents.

This is my attempt to redress that.