HIV/AIDS Skepticism

Pointing to evidence that HIV is not the necessary and sufficient cause of AIDS

Posts Tagged ‘HAART ineffective’

Poison in South Africa

Posted by Henry Bauer on 2008/10/26

Several publications have attempted to calculate the precise life-saving benefits of antiretroviral drugs (Walensky et al., Journal of Infectious Diseases 194 [2006] 11-19; Antiretroviral Therapy Collaboration, Lancet 372 [2008] 293-99; Bhaskaran et al., JAMA 300 [2008] 51-59). All of them are based on rather elaborate computerized models replete with hordes of assumptions, and they deliver outputs that not only differ with one another [numbers are cited in “HAART saves lives — but doesn’t prolong them!?”, 17 September 2008] but that are also at stark variance with plain facts adduced quite directly from observations on patients:
1. The Antiretroviral Therapy Cohort Collaboration (Lancet 2006; 368: 451–58) analyzed data from more than 22,000 patients on HAART and found that the therapy decreased viral load “but such improvement has not translated into a decrease in mortality”; in other words, no life-saving benefit at all.
2. Death statistics for the USA show that, even by 2004, half of all HIV/AIDS patients were dying at or below age 45. Since the introduction of HAART in 1996, both the average time between a diagnosis of AIDS and death and the very slow and steady changes in median age of death from 1982 to 2004, refute the claim that HAART renders “HIV/AIDS” a chronic but manageable disease that offers prospects of virtually a normal life-span [“HAART saves lives — but doesn’t prolong them!?”, 17 September 2008].

Since the observed facts contradict the estimates, the only thing demonstrated by those calculations of supposed benefits from HAART is that one can obtain any desired result from a computer model if one uses a sufficient number of suitable assumptions; and the only thing that consumers of such outputs need to remember is GIGO: Garbage In, Garbage Out [“Antiretroviral therapy has saved 3 million life-years”, 1 July 2008].

To the spurious claims of life-saving benefits from HAART, there has now been added (biology news net) an even more dubious extrapolation: Those supposed benefits have been (mis)applied to calculate how many South African lives could supposedly have been saved, if antiretroviral drugs had been distributed sooner and more widely (Chigwedere et al., JAIDS, online publication ahead of print, 10.1097/QAI.0b013e31818a6cd5) . The overall assumptions are indicated (indicted?) already in the Abstract [emphases added]:

Using modeling, we compared the number of persons who received ARVs for treatment and prevention of mother-to-child HIV transmission between 2000 and 2005 with an alternative of what was reasonably feasible in the country during that period”.

“In 1999, President Thabo Mbeki, under pressure to provide zidovudine (ZDV or AZT) for prevention of mother-to-child HIV transmission (PMTCT) and AIDS treatment, announced that the drug was toxic and dangerous to health and that the government was not going to provide it”; thus implying that AZT is not toxic — or, at least, as though this somehow doesn’t matter: “its side effects were clearly documented and disclosed”, citing for the latter a 1987 paper (Richman DD, Fischl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double-blind, placebo-controlled trial. N Engl J Med. 1987;317:192–197), one of whose authors (Fischl) had subjected Kim Bergalis to such high doses that she died within a couple of years (“The Stories of Those Who Believed in AZT”, Peter Duesberg; several cases are described in “The cure that failed”, Tom Bethell, National Review 10 May 1993).

In case the latter reports of AZT toxicity appear to come from biased sources, have a long look at the official Treatment Guidelines.  One of the “Factors associated with immunologic failure” — i.e., likely causes of destruction of the immune system — is “Medications, both antiretrovirals (ZDV [270], TDF + ddI [271-273]) and other medications” (p. 37). AZT/ZDV is also responsible (Tables 9 & 10) for “Rare but serious cases [i.e., potentially fatal] lactic acidosis with hepatic steatosis”, bone marrow suppression, anemia, mitochondrial toxicity (which can cause hepatic steatosis); in combination with other “life-saving” antiretroviral drugs, “Hypersensitivity reaction that can be fatal” (Table 10). Among the “Potentially Life-Threatening and Serious Adverse Events” (Table 18a), ZDV features under “Lactic acidosis, hepatic steatosis, pancreatitis (severe mitochondrial toxicities)”, “Stevens-Johnson syndrome (SJS), Toxic epidermal necrosis (TEN)”, bone marrow suppression, “Hepatotoxicity (clinical hepatitis or asymptomatic serum transaminase elevation)”. Among the less serious “side” effects “Compromising Quality of Life and/or With Potential Impact on Medication Adherence” (Table 18c), ZDV features as causing “fat maldistribution”.

In other words, contrary to what is implied by Chigwedere et al., ZDV is toxic to a potentially fatal degree. That’s also admitted implicitly by some number of mainstream researchers, even some who claim benefits from HAART, for example, Walensky et al. (Journal of Infectious Diseases 194 [2006] 11-19) whose calculation of supposed benefits of antiretroviral drugs ascribes no benefit at all to AZT/ ZDV treatment from its introduction in 1987 up to the era of HAART. The immediate drop in death rate when ZDV monotherapy was stopped is yet another direct measure of the drug’s toxicity [“HAART saves lives — but doesn’t prolong them!?”, 17 September 2008].

It would be wearisome as well as pointless to cite the innumerable presumptions and assumptions in Chigwedere et al., but I can’t resist pointing to the throw-away phrase highlighted in the following passage:

“we estimated the average life-years that ARV therapy adds to patients with AIDS in Africa. Primary studies done in Africa (including South Africa), a meta-analysis, and a comparison with the developed countries show that other than increased mortality at the start of treatment, patient responses to ARV treatment in Africa are similar to those observed in the developed world. 20”

Reference 20 is Braitstein P, Brinkhof MW, Dabis F, et al; Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration; ART Cohort Collaboration (ART-CC), “Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries”, Lancet 367 [2006] 817-24; the pertinent information is “Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20 532 person-years)”. In other words, in Africa 14.9 of every 100 people treated with HAART die in the first year of treatment, whereas in the developed world only 2 of every 100 people treated with HAART die in the first year of treatment.

Now, that throw-away reference by Chigwedere et al. implies that response to HAART after the initial deaths has been found to be similar in low-income settings to that in high-income ones, but the cited reference doesn’t exactly say that. The ratio of deaths at 9 months is indeed lower than initially, but it is still between 1.5 and 2 times (adjusted and unadjusted hazard ratios respectively) higher in the low-income countries; whether 1.5-2 is  “similar” to 1 is a matter of opinion. Nor is there any obvious reason to assume that the decrease to month 9 will continue thereafter; for example, I might speculate that since the Africans beginning treatment are initially ill, whereas about 70% of those entering treatment in the United States are not ill (asymptomatic HIV-positive with CD4 <200), the Africans would be more likely to succumb to the “side” effects of the drugs, so that the mortality ratio would increase again after its initial decline during the brief exposure of 9 months — almost at once, the most seriously ill Africans succumb to the poisonous drugs, and those who are not so ill succumb more slowly but still appreciably more quickly than in the United States.

In any case, the vastly different criteria for beginning treatment in low- and in high-income countries, and the vast difference in disease burdens of many kinds — both acknowledged in the cited article — suggests that the attempt to extrapolate to low-income settings the benefits calculated for high-income settings is in itself invalid a priori — doubly so, of course, since the benefits calculated for high-income settings are spurious, as shown (see above) by the direct data on >22,000 patients from the Antiretroviral Collaboration and the death statistics for all HIV/AIDS patients in the United States: half the deaths from “HIV disease”, even by 2004, occurred by age 45.

Nor are the technical deficiencies in Chigwedere et al. the only reason to discredit their conclusions. One might also note that the authors lack any credentials to discuss such matters of economic and political policy as “what was reasonably feasible in the country during that period”, which is the whole point of the article. Indeed, one might question the very purpose of publishing these calculations. Even were they impeccably correct technically, they add nothing — and claim to add nothing — of medical or scientific relevance. This is an exercise in propaganda and politics, hardly appropriate for a journal whose raison d’être is described thus:  “JAIDS Journal of Acquired Immune Deficiency Syndromes , non-HIV, and AIDS-related information from all relevant clinical and basic sciences, with a strong focus on molecular biology, cell biology, epidemiology, and clinical virology. Each issue of JAIDS publishes vital information on the advances in diagnosis and treatment of HIV and non-HIV infectious [sic], as well as the latest research in the development of therapeutics and vaccine approaches”. (The reference to “non-HIV” is curious: do they want the Journal to be able to continue even after HIV has been shown not to cause AIDS?) The 3 editors-in-chief specialize in “Basic Science Articles: David D. Ho, M.D. . . . Clinical Articles: Paul A. Volberding, M.D. . . . Epidemiology Articles: William A. Blattner, M.D.”, which brings to mind not only the incongruity of an article on public policy but also what I’ve said about doctors as scientists [“Nobel Prizes Illustrate that Doctors are Not Scientists”, 19 October 2008].

But I’d like to reiterate the main point, which cannot be overemphasized. A decade after the introduction of HAART, we know that its theoretical basis is wrong [“HAART and HIV/AIDS: Dilemmas, Paradoxes, and Errors”, 12 October 2008], and we know that half the people whose lives are being supposedly saved by HAART meet their death by age 45 [“HAART saves lives — but doesn’t prolong them!?”, 17 September 2008]. No amount of sophisticated computer modeling can gainsay those facts.

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HIV/AIDS SCAM: Have antiretroviral drugs saved 3 million life-years?

Posted by Henry Bauer on 2008/07/06

In the previous post [Antiretroviral therapy has SAVED 3 MILLION life-years, 1 July 2008], I showed that the impression conveyed by “millions” is misleading. The claim actually amounts to an estimate that HAART has saved, at an annual cost of about $20 billion, only about 13% of AIDS victims, in other words about 1 in 8, which is hardly what’s implied by the commonly used description of HAART as “lifesaving”.

I referred also in that earlier post to “dishonesty” in the Walensky et al. article. That charge reflects the fact that only a by-the-way sentence on the fourth page of the article modifies drastically the claim, made in the Abstract, of “at least 3.0 million” life-years saved: “Of these, 1,184,851 years have already been realized, and 1,629,041 years are being accrued by current patients”. The claimed 3 million turns out to be less than 1.2 million! Yet that is once again fudged or masked by the last sentence of the article: “Ten years after the introduction of potent combination ART, at least 3 million years of life have been saved in the United States” [emphasis added]. Counting projected future savings as already in hand might not survive an independent audit.

Repeating the calculations in the earlier post with the lower figure of 1.2 million of actually realized savings, we find that there were saved by 2003 not 13% of patients but only 6%, at expenditure of more than $180,000 per saved life-year, or $12.5 million per life; and our productivity in GDP terms then represents a measly return of 0.36% on this human capital. Such are the numbers that Fauci apparently believes to justify current expenditure on HIV/AIDS. One can be sure, moreover, that the computer model was designed and the calculations made with a view to presenting as rosy a picture as possible. If this is the best they can come up with, then it’s time to stop talking about HIV/AIDS as a manageable, chronic but not fatal disease.

Not only is the claimed benefit of treatment much less than impressive, the claim actually lacks any solid foundation whatsoever. It relies on a computer model that makes a number of unjustifiable assumptions, and it ignores such central issues as the acknowledged toxicity of the antiretroviral treatment as well as how the definition of AIDS has changed, and thereby the health-state of people being treated.

Here is the essence of the Walensky article: “The Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model was used to estimate per-person survival benefits. CEPAC is a widely published computer-based state-transition simulation model of HIV disease that incorporates CD4 cell count; HIV RNA level; ART efficacy; OI incidence, treatment, and prophylaxis; and other important clinical information [16–18, 21]. “State transition” means that the model characterizes the progression of disease in an individual patient as a sequence of transitions from one ‘health state’ to another. . . . In the model, the level of HIV RNA determines the rate of CD4 cell count decline, and the absolute CD4 cell count governs the monthly risk of OIs and death”.
One hardly needs to read any further, given that Rodriguez et al. (JAMA 296 [2006], 1498-1506) found a lack of correlation between “HIV RNA level”—otherwise known as viral load—and the rate of CD4 decline. This fact alone would be enough to vitiate the model; but there are also no valid studies of ART efficacy using untreated controls. As to prophylaxis of opportunistic infections, more is said below.

Walensky et al. considered “6 distinct eras of HIV/AIDS treatment from 1989 to 2003”. But about 50,000 AIDS deaths had already been reported up to 1989 (CDC 1990), about 35,000 of those during the AZT monotherapy years of 1987 and 1988. Some (or most or perhaps even all) of those deaths were caused or hastened by the AZT, and those lost life-years should surely be subtracted from the savings calculated from 1989 on, since HAART typically incorporates AZT or an analog of it, albeit at much lower doses than in the monotherapy era. Instead, Walensky et al. apparently seek to hide AZT toxicity by saying that “we excluded the early benefits of antiretroviral mono- and dual-drug therapy when survival benefits were more limited”, a fine illustration of double-speak: “more limited benefits” here stands for “no benefit, just caused harm”.

The first era commences with “prophylaxis for Pneumocystis jiroveci pneumonia (PCP) starting in 1989”, ignoring that Michael Callen and Josef Sonnabend had pioneered prophylaxis against PCP in AIDS victims years earlier. Callen cites data from the Centers for Disease Control and Prevention that more than 30,000 people had died of PCP by February 1989 even though the possibility of prophylaxis had been known since 1977. Callen himself had urged Fauci in May 1987 to recommend prophylaxis, but Fauci refused; nearly 17,000 PCP deaths occurred between May 1987 and February 1989 (pp. 30-31 in Michael Callen, Surviving AIDS, HarperCollins 1990). That is in direct contradiction to the claim that “88% of eligible patients in the pre-ART era were receiving OI [opportunistic infection, includes PCP] prophylaxis” (Walensky et al., p.12). How many of those 30,000 or 17,000 PCP deaths should be subtracted from Walensky’s 3 million — or actually 1.2 million — saved years of life? 30,000 lives lost to PCP, after all, already represent more than 2 million life-years, and even 17,000 lives amount to over a million-and-a-quarter life-years, either of which would wipe out entirely all the life-years claimed to have been saved between 1989 and 2003.

Walensky et al. cite an estimate that only 57% of known “HIV-positive” people are receiving treatment, and they assert that additional life-year-savings would result if more were being treated. But how many of the non-treated are avoiding antiretroviral drugs by choice? Certainly among gay men, knowledge of the fearsome “side”-effects of antiretroviral drugs has been widespread for two decades. Moreover, any reader of the official Treatment Guidelines learns that “In the era of combination antiretroviral therapy, several large observational studies have indicated that the risk of several non-AIDS-defining conditions, including cardiovascular diseases, liver-related events, renal disease, and certain non-AIDS malignancies . . . is greater than the risk for AIDS”. How then could Walensky et al. legitimately ignore these toxicities, as they do: “The analysis did not account for later ART-related toxicities that may result in, for example, cardiac disease or diabetes”. They wave aside the iatrogenic harm from ART even further by opining that “hyperlipidemia reduces overall life expectancy by ~1 month”. When your doctor tells you that your cholesterol is too high and that you should begin a lifelong course of expensive statin drugs — whose deleterious “side” effects also call for regular doses of Coenzyme Q10, which few doctors will tell you, however —, try responding that you have it on good authority that the potential benefit of conquering hyperlipidemia is only about 1 month of extra life. Let me know what your doctor says to that.

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Noted by Walensky et al. is that “after 1992, ~70% of new AIDS diagnoses were made according to a CD4 cell count criterion of <200 cells/mm3 alone”. This criterion for an AIDS diagnosis is unique to the United States, and patients thus diagnosed may display no symptoms of illness. Thus up to 70% of “AIDS” patients receiving antiretroviral drugs in the United States since 1993 have been clinically healthy when they begin “treatment”. It would then be hardly surprising that survival rates increased from the years before 1993 when this CD4-count criterion was introduced, for initially healthy people will surely survive toxic drugs longer than people who are already ill: “projected per-person survival after an AIDS diagnosis increased from 19 months (1.6 years) in the absence of treatment to 179 months (14.9 years) by 2003, a gain of 160 months (13.3 years)” [emphasis added]. The all-knowing computer model can apparently be sure already in 2003 that patients will survive on average into 2018. But even this projection hardly justifies the assertion that AIDS is now “a highly treatable chronic condition”, given that even by 2004 — 8 years into the “lifesaving” HAART era — most deaths from “HIV disease” were still occurring among people around 40 years of age, just as two decades earlier [Table 42, p. 236, in “National Center for Health Statistics: Health, United States, 2007 with Chartbook on Trends in the Health of Americans”, Hyattsville, MD, 2007; see “HIV DISEASE” IS NOT AN ILLNESS, 19 March 2008].

Puzzling is the statement that “Mean per-child survival gains for the averted infections ranged from 60.5 years if the child was born before 1996 (before combination ART) to 45.8 years during 1996-1999, when combination ART was available”. If ART is better, why is the survival gain from it only ¾ of the earlier survival gain from pre-ART prophylaxis of opportunistic infections?

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It also remains for me a continuing mystery that so many AIDS researchers, reviewers of HIV/AIDS manuscripts, and editors of journals that publish this material are so lacking in elementary numeracy as to pepper their articles with numbers like “832,179 years in ART 3”, “2,813,892” years saved, and so on. Numbers no less than words should convey meaning. The only thing conveyed clearly by “2,813,892” is that the writers take computer outputs as sacrosanct and don’t think about what the numbers mean. Those extra digits are not only meaningless, they positively distract the reader, making necessary a mental rounding-off to recognize that the substantive claim is “about 2.8 million”; not many people, after all, are used to digesting 7-digit numbers and savoring their significance. In the Walensky et al. article, the mystery of this abusive mathematical incompetence is only deepened by the fact that the authors’ affiliations include departments of epidemiology and biostatistics.

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Walensky et al. “employed a model-based approach, conducting repeated analyses to explore the clinical consequences of alternative patient-care-innovation pathways”. The whole article deals not with actual patients but with “hypothetical patients”. This fulfills the suggestion, reported in a previous post, that one no longer needs human beings for clinical studies, computers can conveniently substitute [VIRTUAL HIV/AIDS RESEARCH AND TREATMENT, 17 June 2008]. The most convenient thing about this, of course, is that it’s much easier to get the results you want from a computer model you have yourself designed than from observations of real people.

Here’s the point to bear in mind whenever the gurus parade the outputs of their computer models:
A computer model can be guaranteed to mimic reality faithfully only if everything about that reality is already known in every detail. But if that is so, then one doesn’t need a computer model. Computer models are experiments carried out on surrogates of reality, surrogates that are unavoidably simplified and based on assumptions about reality. In the Walensky et al. case, the model incorporates assumptions about what happens to a person with a given viral load and CD4 count under no treatment, and what happens to individuals with given viral loads and CD4 counts under a variety of treatment regimens: all of which are based on guesses, because clinical trials with proper controls have never been carried out to determine properly the parameters needed for such a model. Moreover, as earlier mentioned, the article by Rodriguez et al. found no correlation between “viral load” and subsequent decline in CD4 counts. Further, the article ignores the well established phenomenon of “long-term non-progressors” or “elite controllers”, individuals who demonstrate that being “HIV-positive” does not necessarily lead to destruction of the immune system, illness, and death. How could the fates of non-treated “patients” be modeled when this phenomenon is ignored? When it is not even known what proportion of people are potentially elite controllers?

The outputs of this model deserve no credence whatsoever. The claim of more than 3 million saved life-years is utterly bogus. Even were it not bogus, it would reveal the claimed benefits of antiretroviral therapy to be at best marginal and procured at egregiously excessive cost.

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