Aids HIV FAQ

VIRAL LOAD FRAUD!!!

Question:

> >>  The excuse is AZT/3TC, which was far more effective than any RT >> combo before it, due to mutations causing resistance to one compound >> causing susceptibility to the other. >WRONG! Try again. The only change at this time in the UK was the >avoidance of AZT in any guise, following its widespread exposure >in the media as the true cause of "Aids". (And why no similar >sudden "AZT/3TC drop" in the USA in 1993?)

Wrong indeed! Harris is a tiresome, off-the-wall ex-Californicator who has been exiled to the Utah Asylum/Nuclear Test Range. >    In fact, there was one.  The problem of why the drop in AiDS in the > UK has closely paralled the one on the US, on a % basis, is YOUR > problem to explain.

Not really — Blackdog is the challenger of the establishment "standard of care" Propaganda Ministry and Bullshit Brigade. Fact is, in the developed countries, the infection rate plummetted years ago — in parallel with the drop in AIDS and deaths years later — except for one thing: there should have been even FEWER deaths, but there were still far too many, thanks to a Big FART (Failed Anti Retroviral Therapy). >In fact, those trying to disguise the truth and claim the drop >is due to medical intervention (instead of in spite of it) are >forced to suggest PIs as the cause, and to hope that no one >notices they weren’t available until three years later. >    You’re putting words in my mouth.

Nobody could possibly mimic the stupidity of Harris’ words, so this would be an impossibility. However, Blackdog is 100% correct. Death statistics were hijacked for greed/drug propaganda purposes when they suggested quite the opposite. >  See >the article accompanying that graph in the SGM Quarterly Vol25 >May 1998 for a particularly clumsy example of this. >    What’s the SGM Quarterly?

Stupid Goddamned Murderers Quarterly? Is Harris this month’s creature-feature in the Human Experimentation and Homo-Ethnic Cleansing section? fred

Response:

>>  The excuse is AZT/3TC, which was far more effective than any RT > combo before it, due to mutations causing resistance to one compound > causing susceptibility to the other.   >WRONG! Try again. The only change at this time in the UK was the >avoidance of AZT in any guise, following its widespread exposure >in the media as the true cause of "Aids". (And why no similar >sudden "AZT/3TC drop" in the USA in 1993?)

   In fact, there was one.  The problem of why the drop in AiDS in the UK has closely paralled the one on the US, on a % basis, is YOUR problem to explain. >In fact, those trying to disguise the truth and claim the drop >is due to medical intervention (instead of in spite of it) are >forced to suggest PIs as the cause, and to hope that no one >notices they weren’t available until three years later.

   You’re putting words in my mouth.  See >the article accompanying that graph in the SGM Quarterly Vol25 >May 1998 for a particularly clumsy example of this.

   What’s the SGM Quarterly?                                       Steve Harris, M.D.

Response:

> Maybe some people will think I’m going off on a tangent, but I believe > that this decline in HIV+ patients showing AIDS symptoms or any kind of > symptoms altogether, is an evidence of evolution happening right before > our eyes. All we need is a couple of good mutations to beat this thing. > Obviously, it would be so much easier to pop a pill. > Still, I think every person should take the "HIV test", as you put it. > If not out of respect for yourself, then out of your respect for your > partner.

Caitlin; This implies that the HIV test actually means anything. Here’s a question for you … find proof that the HIV virus has ever been isolated. An electron micrograph of multiple, identical, isolated viral particles would be a good start. Nobody has ever been able to meet this challenge yet (rather surprising, don’t you think?), but you might just be the first! Regards,     David Crowe

Response:

– Hide quoted text — Show quoted text – >In view of another interesting quote of yours I came across, I >would like to have your comments on the spectacular drop in UK >"Aids deaths" since 1993 (see my graph posted earlier). You >claim that this kind of drop is the result of deadly protease >inhibitor "Aids drugs", but as we know these were not available >in the UK or US until late 95 or early 96. (You have admitted >this too.) >So, please treat us to your most imaginative and hilarious >explanation for the UK developments. Your references are as >follows: >  [..] What we want to know is: did the rather slow decline in >  age-specific death rates among HIV positive people through the >  nineties, sudden drop like a rock beginning in 1996, obviously >  due to some new factor introduced at just about that time?  I >  think that history will show that this is so. >History has shown that it dropped just like this in 1993 in the >UK. The only factor is public disbelief. >And that PI combinations were not available until much later: >  [..] Protease inhibitors were not used in HIV infected persons >  until the end of 1995.  It took until the middle of 1996 before >  things really got going.  By contrast, there have been effective >  treatments for most OIs since the mid-80’s.  And these certainly >  haven’t gotten much better from (say) 1994 to 1996.  A big jump >  (drop) in AIDS mortality at that point, needs explaining. >So, let’s hear your excuses.

   The excuse is AZT/3TC, which was far more effective than any RT combo before it, due to mutations causing resistance to one compound causing susceptibility to the other.  But the drop due to PI’s starting in 1996 is bigger.  Or will be when the statistics are completely in (which we’ll know has happened when the updated number for year doesn’t change for two successive years).                                            Steve Harris, M.D.                                           Steve Harris, M.D.                                      Steve Harris, M.D.

Response:

>  The excuse is AZT/3TC, which was far more effective than any RT > combo before it, due to mutations causing resistance to one compound > causing susceptibility to the other.  

WRONG! Try again. The only change at this time in the UK was the avoidance of AZT in any guise, following its widespread exposure in the media as the true cause of "Aids". (And why no similar sudden "AZT/3TC drop" in the USA in 1993?) In fact, those trying to disguise the truth and claim the drop is due to medical intervention (instead of in spite of it) are forced to suggest PIs as the cause, and to hope that no one notices they weren’t available until three years later. See the article accompanying that graph in the SGM Quarterly Vol25 May 1998 for a particularly clumsy example of this. So far, you have failed to answer the question, Harris.   > But the drop due to PI’s starting in 1996 is bigger.  

How on earth can it possibly be any more spectacular than the drop illustrated in the UK figures? "Aids deaths" go into free-fall as soon as the superstition is exposed, especially to the diagnostically targeted groups. If you are hoping the same phenomenon in the US can be disguised as due to PIs, how are you going to explain those UK figures? All you have done here is dig yourself into an even bigger hole.  John —   ‘More than GBP1 billion has been poured into Aids health work and campaigning as a result of claims that Britain was on the verge of an epidemic. Yet the numbers concerned, while each of them is an individual tragedy, have been minuscule compared with other diseases.   In total about 9,000 people have died of Aids since 1984 – far fewer than the number of women killed every year by breast cancer.’                                            Daily Express 15-Jan-98

Response:

> > john (himself) is on record as telling the group that i am employed by > the "aids establishment" for volunteer work i do with the national > hemophilia foundation.  [..]

(with his "brillant edititng skills", john attempts to avoid. the end of the perceding paragraph reinserted)) " he lives in the u.k., i live in pennsylvania. when challanged to substantiate his statement (numerous times!!!!), he ignored the request.  he also ignored the request to apologize for this dishonesty. so, readers of this group are expected to believe anything he posts?" > You admitted your employment in the "Aids" racket.

employ defined: (noun) paid occupation.  where and when?  a reference, please. >You have claimed it > is without benefit to yourself.

no, i have stated that it is without benefit to me.  it is your continued unfounded claim that i am compensated by the ‘"Aids" racket’. this is another request to substantiate your accusation that the national hemophilia foundation is a front for the ‘"Aids" racket’.     >You promote commercial products, with > no known value but deadly effects.

another unfounded accusation.  the only thing i promote is a person’s responsibility to educate themself about hiv/aids and makes choices based on the best information they can get.   >I advised you to keep an eye on your > legal situation; advice that still stands.

speaking of legal situations, would you care to comment on your accusations of fraud against graham ross and sue theakell?  as you know, graham ross is the lawyer that got the uk government to settle with the uk hemophilia population over their infection with hiv through the use of factor clotting concetrates.  the treakell’s were one of the named litigants.  these two are also the subjects of the "famous murder by azt trial" you keep referring to. i thought not! > p.s.  happy fourth of july! isn’t this the celebration of the defeat > of the british by the colonists? > USA:390,000, superstition still killing. UK:9,000, superstition ancient > history. Happy 4th of July, people.

a re-colonization effort? >  John > — > "Actually, that was a great British victory.  Colonists of British > origin fighting for age-old British values against Hessian mercenaries > under a German king.  No wonder we won."                         anon

i guess history, like "aids science", is in the eye of the beholder. have a wonderful time in france.  one of my anti anti-viral friends just got back from europe and said france was the highlight of his trip. take care, be well. donpaul lucas (not a pseudonym) chair, education and information committee of the national hemophilia foundtion hemophiliac, 15 years hiv infected, 11 years medication experience [currently on azt (for over four years), 3tc (three years) and crixivan (two years) and asymptomatic.

Response:

- Hide quoted text -- Show quoted text - > The "HIV" promoters always work on personal attacks, as they lack > any way to respond to the facts. Harris has toned down his comedy > German accent, that he used to employ in discussing Duesberg, for > example, because readers found it too blatantly desperate. But in > essence his whole attitude is one of ad hominem disparagement, like > the rest of them. > I am in really good health. I have never taken an "HIV test" and I > never would. I considered it in the mid-eighties but luckily the > excellent dissident information available in the UK, such as the > influential Meditel Productions films and the Sunday Times articles > convinced me the whole thing was a scam. The statistics for "Aids" > in the UK show that it also convinced thousands more people to > give the racket a wide berth, and we have been proved absolutely > right. The graph of UK "Aids deaths" shows a steep decline in > victims offering themselves for sacrifice after the truth became > known (that AZT was the true cause of our minimal "Aids") by 1993, > well before any combo drug intervention was available. No informed > person would submit to an "HIV test" now! > (Dr Harris is also on record telling the group that I have taken a > test, and that I got a positive result. I live in the UK. He lives > in Utah. When challenged to substantiate his statement, he quickly > backed down. This is a man Utah residents are expected to trust as > a doctor!) >  John

I'm glad you're in good health. I wish every person on Earth could make this statement. Maybe some people will think I'm going off on a tangent, but I believe that this decline in HIV+ patients showing AIDS symptoms or any kind of symptoms altogether, is an evidence of evolution happening right before our eyes. All we need is a couple of good mutations to beat this thing. Obviously, it would be so much easier to pop a pill. Still, I think every person should take the "HIV test", as you put it. If not out of respect for yourself, then out of your respect for your partner. caitlin

Response:

>  Cite the message or shut up.

First you admit it, then you deny it. Last time this came up you were markedly were less contradictory: > Is this a good time to remind you that I have had no > response so far to my offer of a bet? You will remember that some > time ago you categorically advised the group, on the basis of > your deep scientific erudition and wide experience as a doctor, > [Harris:] >   Actually, that was on my basis of my understanding of human > nature.  I could be wrong, of course, but there’s no way to know.

You were wrong, as usual, *and* you were not prepared to put your ‘understanding of human nature’ (huh!) to the test. In view of another interesting quote of yours I came across, I would like to have your comments on the spectacular drop in UK "Aids deaths" since 1993 (see my graph posted earlier). You claim that this kind of drop is the result of deadly protease inhibitor "Aids drugs", but as we know these were not available in the UK or US until late 95 or early 96. (You have admitted this too.) So, please treat us to your most imaginative and hilarious explanation for the UK developments. Your references are as follows:   [..] What we want to know is: did the rather slow decline in   age-specific death rates among HIV positive people through the   nineties, sudden drop like a rock beginning in 1996, obviously   due to some new factor introduced at just about that time?  I   think that history will show that this is so. History has shown that it dropped just like this in 1993 in the UK. The only factor is public disbelief. And that PI combinations were not available until much later:   [..] Protease inhibitors were not used in HIV infected persons   until the end of 1995.  It took until the middle of 1996 before   things really got going.  By contrast, there have been effective   treatments for most OIs since the mid-80’s.  And these certainly   haven’t gotten much better from (say) 1994 to 1996.  A big jump   (drop) in AIDS mortality at that point, needs explaining. So, let’s hear your excuses. You have a few days to dream something up. Make it good, now.  John —   " I have heard it rumored that women sometimes participate in anal intercourse, Sue. It’s pretty darned tough to separate these variables in epidemiologic studies."                          Steve Harris, M.D.

Response:

- Hide quoted text — Show quoted text -> > So, many of these HIV+ women did not have HIV-1 RNA or HIV-1 DNA in > > their breast milk. And, women who had HIV-1 RNA in their breast milk did > > not necessarily have HIV-1 DNA (and vice-versa). > And these are the women who are expected to poison themselves > and their babies with AZT? How can such malpractice ever be > justified? >  John > Because babies can also get infected during delivery. > Frank

Infections are reduced or eliminated through Caesarians and washing the birth canal. Also, the AZT studies didn’t follow the babies long enough to determine if they developed antibodies up to a year after birth, so it is possible that AZT simply lowered the baby’s ability to manufacture antibodies to the virus it may have been infected with at birth and went "undetected". The high-risk mother factors/preventive practices were known BEFORE AZT arrived on the scene, but wasn’t announced as "proven" until long after AZT became the pregnancy "standard" — and quite recently. One must wonder if these AZT pregnancy trials were actually using other extraordinary measures for the women taking AZT (you know, just like ACTG016!!!) such as caesarians for women with the highest viral load and washing of the birth canal before delivery. This, of course, is EXACTLY what happened in African studies — like the one that eliminated the placebo group as "unethical" despite the fact that the current standard of care was NO antivirals! Also, the women who transmit to their babies are those with the highest viral load. Unexplainably, the viral load test is NOT the determinant of treatment — THEY ARE ALL BEING TREATED REGARDLESS OF TRANSMISSION RISK AND TERATOGENICITY!!! Finally! After 10 long years of hard research, they FINALLY thought they had a use for AZT!!! (not!) What a fucking scam!!! fred

Response:

– Hide quoted text — Show quoted text ->  There’s no evidence for this happening, even on the old long course > of AZT, which was AZT for half of pregnancy.  The new standard of care > is use of AZT by the mother for only a few weeks (4, I believe) before > expected delivery. >You have absolutely no idea of the consequences of this malpractice. >This kind of experimentation is deeply contemptible. Those involved >must expect the harshest sentence the criminal law allows. > John

   Hey, but, they know where to find me.  You’re the one posting anonymously.  Which of us is most afraid of the backlash when people realize how many deaths have been caused by misinformation?    Freedom of speach is not quite so well protected in your country, I understand.  Where you are, the libel laws have teeth.  If I was you, I’d look into it.                                      Steve Harris, M.D.

Response:

>Infections are reduced or eliminated through Caesarians >and washing the birth canal. Also, the AZT studies didn’t >follow the babies long enough to determine if they >developed antibodies up to a year after birth, so >it is possible that AZT simply lowered the baby’s >ability to manufacture antibodies to the virus it >may have been infected with at birth and went >"undetected".

   No, it’s not possible, since the studies don’t look at antibodies at all, since they are worthless in telling whether infants are infected with HIV (unless you do the very new IgE stuff, which has yet to be generally accepted).  All babies born of HIV+ mothers will be HIV positive, whether infected or not.    Such trials measure HIV vertical transmission by viral culture from babies, and PCR. >This, of course, is EXACTLY what happened in African >studies — like the one that eliminated the placebo >group as "unethical" despite the fact that the current standard >of care was NO antivirals!

   The current standard of care sucked.  Ethically, you can argue it either way.  If the drug company had enough money to do the study, they had enough to treat everybody in it. >Also, the women who transmit to their babies are those >with the highest viral load. Unexplainably, the viral >load test is NOT the determinant of treatment — THEY ARE >ALL BEING TREATED REGARDLESS OF TRANSMISSION RISK AND >TERATOGENICITY!!!

   But Fred, you complain so much when viral load is the determanant of treatment.  Dispite the fact that it’s a big factor in sexual transmission also. >Finally! After 10 long years of hard research, they >FINALLY thought they had a use for AZT!!! (not!) >What a fucking scam!!!

   They do have a use for AZT.  6 weeks of it cuts chance of passive HIV to the child by 50%.    You seem to use the word fuck in all your posts, these days. Something chewing at your frontal lobes?  Writing while drunk is not pretty, Fred.                                        Steve Harris, M.D.

Response:

>  Hey, but, they know where to find me.  You’re the one posting > anonymously.  Which of us is most afraid of the backlash when people > realize how many deaths have been caused by misinformation?

They know where to find me too. Or at least how to. I am not posting through an anonymous remailer – simply limiting the nuisance that idiot "HIV" believers might cause. >  Freedom of speach is not quite so well protected in your country, I > understand.  Where you are, the libel laws have teeth.  If I was you, > I’d look into it.

Would you? British libel suits have a nasty way of backfiring on their originators, as more than one giant US concern has discovered to its considerable cost. The idea that the criminal "Aids" racket would voluntarily place itself into an open courtroom is a outcome very much to be wished. 400,000 murders in the USA alone. 9,000 in the UK, before public disbelief stopped the madness. Is it likely these crooks would pay to have themselves incriminated in public? They have had plenty of opportunities. They’re running very scared indeed.  John —   "Meanwhile, let us hope that the country is not confronted with a real epidemic in the near future: after the disinformation the government has told us about Aids, who would believe it?"                  Andrew Neil, editor, The Sunday Times, 23 June 1996.

Response:

> They know where to find me too. Or at least how to. I am not posting > through an anonymous remailer – simply limiting the nuisance that > idiot "HIV" believers might cause. >  John

Is John an HIV+ person in denial?  Maybe that’s a terrible question to ask but I had to.

Response:

>Is John an HIV+ person in denial?  Maybe that’s a terrible question to >ask but I had to.

   We suspect so.  Same for Shaw.  But hard to prove.                              Steve Harris, M.D.

Response:

> Is John an HIV+ person in denial?  Maybe that’s a terrible question > to ask but I had to.

The "HIV" promoters always work on personal attacks, as they lack any way to respond to the facts. Harris has toned down his comedy German accent, that he used to employ in discussing Duesberg, for example, because readers found it too blatantly desperate. But in essence his whole attitude is one of ad hominem disparagement, like the rest of them. I am in really good health. I have never taken an "HIV test" and I never would. I considered it in the mid-eighties but luckily the excellent dissident information available in the UK, such as the influential Meditel Productions films and the Sunday Times articles convinced me the whole thing was a scam. The statistics for "Aids" in the UK show that it also convinced thousands more people to give the racket a wide berth, and we have been proved absolutely right. The graph of UK "Aids deaths" shows a steep decline in victims offering themselves for sacrifice after the truth became known (that AZT was the true cause of our minimal "Aids") by 1993, well before any combo drug intervention was available. No informed person would submit to an "HIV test" now! (Dr Harris is also on record telling the group that I have taken a test, and that I got a positive result. I live in the UK. He lives in Utah. When challenged to substantiate his statement, he quickly backed down. This is a man Utah residents are expected to trust as a doctor!)  John —   "We have a level of concern that is out of all proportion to the real risk, and that has merely continued and been boosted at various times over the last ten years. People have a greater chance of winning the National Lottery or being struck by lightning." Dr M Fitzpatrick, interviewed on ‘What’s The Story’ about "Aids" establishment lies in the media.   [UK Ch 5, Sunday, 22 June, 1997]

Response:

> Infections are reduced or eliminated through Caesarians > and washing the birth canal. Also, the AZT studies didn’t > follow the babies long enough to determine if they > developed antibodies up to a year after birth, so > it is possible that AZT simply lowered the baby’s > ability to manufacture antibodies to the virus it > may have been infected with at birth and went > "undetected".

No fred, wrong on at least two counts.  First the infants were followed to 18 months after birth before deciding they were uninfected.  Second they were also studied virologically. I am not saying that AZt might not have altered antibody production, just that this is not the explanation of the results.

Response:

>>  There’s no evidence for this happening, even on the old long course > of AZT, which was AZT for half of pregnancy.  The new standard of care > is use of AZT by the mother for only a few weeks (4, I believe) before > expected delivery. >You have absolutely no idea of the consequences of this malpractice. >This kind of experimentation is deeply contemptible. Those involved >must expect the harshest sentence the criminal law allows.

…and shareholders would be wise to sell off their Glaxo stock before the bomb hits – Hide quoted text — Show quoted text -> John >–   >’In 20 samples, a designated gene related to an HIV protein could not be >found, showing there was no virus in the blood. This suggested the sample >for the initial HIV test for each baby was contaminated. Pieces of DNA can >become airborne during transfers or can enter the wrong container in other >ways, Frenkel said.   >   In 17 samples, the gene for the HIV protein did not match the gene in >the mother’s sample. Virus from another infant had contaminated the sample, >the scientists concluded’.  The Seattle Times, May 14, 1998, NEWS Pg.A3

Response:

>>And babies can get cancer or birth defects at any time during their >development when their mothers or (after birth) they are being >"treated" >(poisoned?) with AZT. >- David Crowe >   There’s no evidence for this happening, even on the old long course >of AZT, which was AZT for half of pregnancy.  The new standard of care >is use of AZT by the mother for only a few weeks (4, I believe) before >expected delivery.

Know what, Harris? If you’re married and your wife should have a child & the child be diagnosed as HIV+, you should practice what you preach and start the Retrovir syrup ASAP. Abhorrent as the results would be, it would serve you right for your ignorance. *For anyone else, avoid given deadly poisons to your child* http://www.duesberg.com/cgi-bin/htsearch

Response:

>And babies can get cancer or birth defects at any time during their >development when their mothers or (after birth) they are being "treated" >(poisoned?) with AZT. >- David Crowe

   There’s no evidence for this happening, even on the old long course of AZT, which was AZT for half of pregnancy.  The new standard of care is use of AZT by the mother for only a few weeks (4, I believe) before expected delivery.

Response:

>  There’s no evidence for this happening, even on the old long course > of AZT, which was AZT for half of pregnancy.  The new standard of care > is use of AZT by the mother for only a few weeks (4, I believe) before > expected delivery.

You have absolutely no idea of the consequences of this malpractice. This kind of experimentation is deeply contemptible. Those involved must expect the harshest sentence the criminal law allows.  John —   ‘In 20 samples, a designated gene related to an HIV protein could not be found, showing there was no virus in the blood. This suggested the sample for the initial HIV test for each baby was contaminated. Pieces of DNA can become airborne during transfers or can enter the wrong container in other ways, Frenkel said.      In 17 samples, the gene for the HIV protein did not match the gene in the mother’s sample. Virus from another infant had contaminated the sample, the scientists concluded’.  The Seattle Times, May 14, 1998, NEWS Pg.A3

Response:

- Hide quoted text — Show quoted text -> > So, many of these HIV+ women did not have HIV-1 RNA or HIV-1 DNA in > > their breast milk. And, women who had HIV-1 RNA in their breast milk did > > not necessarily have HIV-1 DNA (and vice-versa). > And these are the women who are expected to poison themselves > and their babies with AZT? How can such malpractice ever be > justified? >  John > Because babies can also get infected during delivery.

And babies can get cancer or birth defects at any time during their development when their mothers or (after birth) they are being "treated" (poisoned?) with AZT. – David Crowe

Response:

> So, many of these HIV+ women did not have HIV-1 RNA or HIV-1 DNA in > their breast milk. And, women who had HIV-1 RNA in their breast milk did > not necessarily have HIV-1 DNA (and vice-versa).

And these are the women who are expected to poison themselves and their babies with AZT? How can such malpractice ever be justified?  John — "The HIV hypothesis ranks with the ‘bad air’ theory for malaria and the ‘bacterial infection’ theory of beriberi and pellagra. It is a hoax that became a scam."  Dr. Bernard Forscher, former editor of the Proceedings of the (U.S.) National Academy of Sciences.

Response:

> > So, many of these HIV+ women did not have HIV-1 RNA or HIV-1 DNA in > their breast milk. And, women who had HIV-1 RNA in their breast milk did > not necessarily have HIV-1 DNA (and vice-versa). > And these are the women who are expected to poison themselves > and their babies with AZT? How can such malpractice ever be > justified? >  John

Because babies can also get infected during delivery. Frank

Response:

> "Firstly, it is unclear whether circulating plasma viral products (RNA, > viral protein or intact virions) all give internally consistent > results."

In a paper entitled "Cell-Free Human Immunodeficiency Virus Type 1 in Breast Milk" (J Inf Dis 177:34-9, 1998) breast milk was taken from 75 HIV+ women. HIV-1 RNA was detected in breast milk from 29 women, and not in 46. Of the 29 women with HIV-1 RNA in their breast milk only 20 had detectable HIV-1 DNA. Of the 46 women without HIV-1 RNA in their breast milk 44 were monitored for HIV-1 DNA and, of these 44, only 25 had HIV-1 DNA. So, in summary:                 HIV+   100%                       |                      /                     /                      /                       /                        /           HIV-1 RNA     +           –             (63%)           (47%)             /             /                /             /       HIV-1 DNA +       –       +        -          (27%)   (12%)   (34%)   (26%) So, many of these HIV+ women did not have HIV-1 RNA or HIV-1 DNA in their breast milk. And, women who had HIV-1 RNA in their breast milk did not necessarily have HIV-1 DNA (and vice-versa). I only wish that they had tested a control sample of HIV- negative women, I bet you that similar ratios would have been seen! Also, it is worth noting that not a single woman in this sample was classified as having AIDS, although a number had the vaguely defined "HIV disease" or "HIV symptoms", which can be as vague as "history of skin rash". – David Crowe

Response:

Tim Peto article: Nice evaluation of the relevancy of surrogate markers by Tim Peto, an expert in this area. He makes some very interesting comments on circulating viremia as measured by the viral load tests. He makes the following four points about measuring plasma viremia: "Firstly, it is unclear whether circulating plasma viral products (RNA, viral protein or intact virions) all give internally consistent results." "Secondly, it is unclear whether plasma viral load is the main measure of HIV disease activity." . . . "Thirdly, the quantitative relationship between changes in viral load and drug efficacy is completely unknown." . . . "Lastly, the relationship between drug efficacy and changes in viral load may differ between different classes of antiviral drugs." Peto concludes his article by stating "At present there is no convincing evidence that the current surrogate markers can be reliably used to predict the clinical efficacy of new treatments. Indeed proper validation will probably need to await the arrival of much more effective clinical treatments. Meanwhile, surrogate marker responses should only be used in the early assessment of new drugs, in order to help the selection of new drug regimens for large scale testing in long term clinical trials." Peto T. Surrogate markers in HIV disease. Journal of Antimicrobial Chemotherapy 1996, May, 37(Suppl. B):161-170. Abstract: The use of surrogate markers in HIV disease is an attractive method of assessing the efficacy of new treatments more quickly than by using clinical end-points. The characteristics of an ideal surrogate marker and the theoretical dangers of extrapolating properties from one class of drug to another are described. These characteristics are compared with the use of the CD4 lymphocyte count, which so far has been the most widely studied. Results from 14 randomized controlled trials of nucleoside analogues are used to compare the comparative changes of CD4 counts with the differential rates of progression to AIDS and differences in survival. There was some correlation between CD4 count changes and development of AIDS, particularly in the short term trials. In contrast, there was little correlation between CD4 counts and overall survival. Comparative studies between clinical end-points and quantitative measures of plasma viraemia have not yet been completed. In conclusion, no surrogate marker has yet been shown to be useful in predicting the efficacy of anti-HIV treatment. Until surrogate markers are validated against the results from long term clinical trials, they should only be used to screen new drugs warranting further study rather than to draw conclusions on the clinical efficacy of new treatments. Page 163-4: COMPARISON OF DIFFERENT TREATMENTS. Surrogate markers can be used to determine the clinical efficacy of a new treatment. This is the most stringent requirement for a surrogate marker. It has been suggested that for a surrogate marker to be valid ". . . a test of the null hypothesis of no relationship [of the marker] to the treatment groups must also be a valid test of the corresponding null hypothesis based on the true endpoint." For a surrogate marker to satisfy this, changes over time must correlate with the risk of progression and any effect of treatment on the risk of clinical progression must be explainable and predictable by the effect of treatment on the markers. For example, CD4 lymphocyte counts are a valid marker only if the whole treatment effect of zidovudine is reflected by changes in the CD4 counts. Unfortunately observational studies have failed to show this. Even this stringent requirement of a surrogate marker has its limitations. It is also important to have data on the size of a treatment benefit in order to determine whether the benefit outweighs its toxicity and cost. Such a quantitative relationship between changes in the surrogate marker and the clinical outcome is difficult to predict. A common fallacy is to assume that the relationship between a prognostic marker and outcome, obtained from natural history studies, can be used to predict the effect of a treatment induced change in the marker. The different possible relationships which might be found between a change in a surrogate marker and the clinical outcome is represented schematically in Figure 1. Each relationship represents the response of the same marker to different classes of drugs. The horizontal axis represents the effect of treatment on the value of the drugs. The horizontal axis represents the effect of treatment on the value of the surrogate marker while the vertical axis represents any improvement (or worsening) in clinical outcome. In the diagram some responses are compatible with a ‘Prentice’ marker. For example drug ‘O’ in ineffective with no effect on the marker nor on outcome. Drug ‘I’ produces a dose-response curve of an ideal surrogate marker in which there is a continuous and predictable quantitative relationship between the change in the marker and clinical effect. Drug ‘H’ produces a large change in the marker with little benefit, while drug ‘G’ is clinically effective but only has a marginal impact on the surrogate marker. Drug ‘B’ worsens both outcome and the marker. The other drugs (A,C,E,D) do not follow the expected surrogate-clinical relationship. Drugs E and C affect clinical outcome without changing the marker. Pathophysiological explanations are not difficult to conceive: for instance, a clinical effective drug (E) could affect the distribution of lymphocytes (or virus) between the circulation and other tissues. An inactive drug (C) could be dangerously toxic. Other clinically ineffective drugs could simply affect the marker as an ‘epiphenomenon’. Drugs may have the opposite effect than expected (for example, A and D). Drug D looks attractive as judged by the surrogate response but is clinically deleterious. This pattern of response has often, and dramatically, been shown in other diseases. In particular, in heart disease, flecainide was shown to prevent arrhythmias which are prognostically a dangerous sign but perversely was shown in a large randomised study to increase mortality (Cardiac Arrhythmia Suppression Trial, 1989). Drug A is an important class of drug which likely to have a novel action producing clinical benefit in a manner that worsens the prognostic markers. It is not implausible that a new ‘miracle drug’ which kills all HIV infected cells would cure the patient but might produce a transient although profound fall in circulating CD4 cells and an intense rise in the measured plasma viral load. Such a paradoxical effect on prognostic markers is illustrated by the effect on haemoglobin and white blood counts of chemotherapy for the treatment of leukaemias. The response of a surrogate marker to a new class of anti-HIV therapy should therefore be interpreted with caution until its relationship with the outcome has been determined in clinical trials. Pages 165-166: CIRCULATING VIRAEMIA. The advantages of measures of viral load are that they offer a pathophysiologically plausible index of disease activity and that they are easy to quantify. They are now commonly used to screen the clinical activity of new drug combinations. Repeated measurements can be easily performed on each patient. Repeated measurements can be easily performed on each patient and changes in viral load accurately followed over weeks and months. Therefore, only a small number of patients need to be studied to obtain a repeatable results. The disadvantages, however, of the assays are fundamental. Firstly, it is unclear whether circulating plasma viral products (RNA, viral protein or intact virions) all give internally consistent results. Secondly, it is unclear whether plasma viral load is the main measure of HIV disease activity. Recent work has suggested that the main reservoir of HIV disease is in the lymph nodes. Although observational studies suggest that plasma viral load gradually increases with disease progression, the importance of circulating viral load is unclear. It is possible that most viruses reside in tissue cells and only use circulatory cells to traffic between tissues. It is also possible that cell-free viral load represents the products of cell death and therefore might be expected to rise in the face of effective anti-HIV therapy. Thirdly, the quantitative relationship between changes in viral load and drug efficacy is completely unknown. There is a reasonable belief that the more viral load is suppressed and the more prolonged the trough, the better. However, this assumption has never been tested. Recent studies on the kinetics of viral replication suggest that viral turnover is very marked. This makes any inference from viral load measurements to total body viral replication difficult. For instance, drugs which increase the clearance of virions from the plasma will lead to an observed fall in virion concentration, which in turn may lead to a false conclusion that total body viral replication has been suppressed. Lastly, the relationship between drug efficacy and changes in viral load may differ between different classes of antiviral drugs. Although a rational relationship may exist between viral load changes and efficacy for nucleoside analogue reverse transcriptase inhibitors, the same relationship may not hold for other reverse transcriptase inhibitors, let alone protease inhibitors. Clearly, the expected short term effect on circulating viral load of effective gene therapy strategies or other novel treatments (for example, the transfer of HIV 1 specific cytotoxic lymphocytes), is completely unclear. The interpretation, therefore, of changes in the markers of disease activity with novel treatments is difficult and may lead to major errors. Current large scale randomised clinical trials of combination treatment (DELTA and ACTG 175) are designed to compare changes in viral … read more »

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