HIV/AIDS Skepticism

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


Posted by Darin Brown on 2008/06/11

Someone recently alerted me to a 2006 paper comparing adverse events on “continuous” vs. “interrupted” ARV therapy:

“CD4+ Count-Guided Interruption of Antiretroviral Treatment: The Strategies for Management of Antiretroviral Therapy (SMART) Study Group”, NEJM, Volume 355:2283-2296, November 30, 2006, Number 22

The study was trumpeted in the media as the death knell for so-called “interrupted” or “intermittent” ARV therapy, following the conclusion:

“Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy.”

The original study was intended to last 6-9 years:

“We calculated that 6000 patients would need to be enrolled for the study to have a statistical power of 80% to detect a 17% relative reduction in the rate of opportunistic disease or death from any cause in the drug conservation group as compared with the viral suppression group, with a two-sided alpha level of 0.05. Follow-up was to continue until 910 primary end points had occurred (estimated to be at least 6 years for each participant), assuming an event rate in the viral suppression group of 1.3% in each of the first 2 years and 2.6% per year thereafter.”

but was stopped short after a mean patient follow-up of just 16 months, for “ethical reasons”:

“On January 10, 2006, at its sixth meeting, the board recommended stopping enrollment in the SMART trial because of a safety risk in the drug conservation group and because it appeared to be very unlikely that superiority of the drug conservation treatment would be shown. On January 11, 2006, investigators and participants were notified of these findings, enrollment was stopped, and participants in the drug conservation group were advised to restart antiretroviral therapy.

What I found most revealing about this study was:

“Only 8% of deaths were due to opportunistic disease.”

The cognitive dissonance here is astounding.

Among all patients, grade 4 events occurred about 3.5 times as often as opportunistic disease: a total of 89 patients experienced any type of opportunistic disease; by contrast, a whopping 321 patients experienced grade 4 events.

Even more shocking is the following: out of all 85 patients who died, more than 5 times as many experienced grade 4 events as compared to opportunistic diseases, because 37 of the 85 patients who died experienced grade 4 events, compared to only 7 who experienced opportunistic diseases.

Opportunistic diseases did occur about 3.5 times as often in the DC (drug conservation) group as in the VS (viral suppression) group (69:20), but only 7 of these 89 patients died (8%), 4 from the DC group and 3 from the VS group. By contrast, grade 4 events occurred slightly more often in the DC group as in the VS group (173:148), but 37 of these 321 patients died (12%).

This also means that out of all patients who died, between 41 and 48 patients (48-56%) died due to causes that were either unknown or not related to either opportunistic diseases or grade 4 events. I wonder why the researchers didn’t stop to ponder this incredibly bizarre finding.

Let’s put these numbers into perspective: We have a study on giving ARV to HIV patients, and 5 times as many have drug reactions as AIDS defining illnesses, and this fact doesn’t even register with the authors of the paper? HALF of all deaths have nothing to do with AIDS or ARVs, and this bizarre fact doesn’t register with the researchers either?

The half of all deaths having nothing to do with AIDS or ARVs is several times higher than the average national mortality rate for all Americans among that age group. Why are they dying so much? They can’t blame their low CD4 counts, because their deaths weren’t AIDS related. They can’t even blame the drugs! Obviously, simply being told you’re HIV positive and have a low CD4 count greatly increases your probability of dying from things that have absolutely nothing to do with HIV or CD4 counts… very strange.

Never mind that the whole explanation why this study supports “continuous” therapy is prima facie absurd. The reasoning goes something like this: After controlling for other factors, lower CD4 counts and higher viral load were associated with higher risk of adverse events, and so the reason the patients on “interrupted” therapy had more adverse events was because they weren’t getting enough ARVs to keep HIV viral load in check, to keep their CD4 counts high enough to stave off the adverse events caused by the ARVs in the first place.

Try wrapping your mind around that one!

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  1. hhbauer said


    Many thanks for this. The SMART study was mentioned in the text of Baker et al., CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection, AIDS 22: 841, which I discussed in DEATH, ANTIRETROVIRAL DRUGS, and COGNITIVE DISSONANCE, 9 May 2008,, but no citation was given in the list of references and I had not followed it up. It is an even more astonishing instance of not only cognitive dissonance but also technical incompetence: surely it’s axiomatic that when studies are cut short, they violate the protocol and statistical inferences become invalid. Indeed, in long-standing controversies over psychic phenomena, a central point has been that doing a study with “optional stopping” permits one to obtain just about any desired result.

  2. Dave said

    Excellent analysis, Henry.

    When you go through life as a hammer, everything begins to look like a nail.

    When you go through life as drug pusher, every little ailment must be attributed to the underlying disease.

    Perhaps, these authors should re-assess the term “therapy”

  3. Gene said

    Congratulations, Darin, on an excellent demonstration of not only how to lie with statistics, but — looking behind the curtain — we see that this shock-horror field of ARVs has spawned a “new generation” of professionalized incompetence.

    They have learned all the appropriate lessons within the lucrative practice of cut-and-paste AIDS science.

  4. MacDonald said

    Another rerun of a Cognitive Dissonance Classic has just come out. The researchers behind “Changes in the Risk of Death After HIV Seroconversion Compared With Mortality in the General Population” underscore the importance of their study with this astounding claim:

    “To our knowledge, no study to date has made a comparison of mortality among HIV-infected and uninfected individuals adjusted for duration of HIV infection, and our results provide estimates, hitherto unavailable, of the cumulative excess probability of death as duration of HIV infection increases.”

    Leaving aside the hard-to-fathom circumstance that never before in a gazillion similar HIV-studies has it occurred to anyone to adjust for duration of “infection”, the study, by virtue of its basic premise, concludes exactly the same as the gazillion other studies based on the same premise have concluded, and will continue to conclude, namely that mortality among HIV-test positives has decreased since the ’80s and the early ’90s:

    “We found that the gap in mortality rates between HIV-infected individuals in our study and the general population narrowed in every calendar period from 1996 onward.”

    Everybody famliar with HIV science will have recognized the standard ploy used to guaranteed the main conclusion: The AIDS Era is by arbitrary convention divided into a Pre-HAART Era (pre-1996) and a HAART Era (post-1996). This naming-and-dating-trick allows the researchers to disregard all other factors, such as changing definitions of AIDS or the fact that the dramatic decrease in AIDS deaths started before HAART came into general use. This leaves the conclusion that, since there are fewer deaths in the HAART Era than in the Pre-HAART Era, HAART must be the direct cause. It is almost comical to watch how this unassailable basic premise shields the researchers from all alternative explanations to the numerous contradictions they encounter — that is, if it allows them to detect contradictions at all — and unfailingly allows them to reach identical completely unwarranted pseudo-conclusions. For example, the authors of this paper “conclude”:

    “Mortality rates for HIV-infected persons have become much closer to general mortality rates since the introduction of highly active antiretroviral therapy “.

    Note, this is NOT a conclusion; it is simply the premise restated. The take-home message is articulated by study author Kholoud Porter, PhD, in an accompanying interview

    ‘Porter said the study “underscores the importance that people are identified and treated early”‘.

    But even if we accept the first premise/conclusion, there is just no basis for accepting the second, not least because the study has not explored any alternative explanations. One cannot conclude without argument. The authors are well aware that they have not accounted for a number of important factors, and they state it clearly in several places, most prominently in their Comments:

    “Our study has some limitations. Ideally we would like to quantify the excess mortality associated with HIV infection. To this end, we have compared mortality in CASCADE with that in the general population. Although we matched by age, sex, calendar time, and country, it is likely that HIV-infected individuals in our study differ from the general population in other ways. Rates of smoking have been shown to be high among some HIV-infected populations30; other risk behaviors, socioeconomic factors, and race/ethnicity are also likely to differ among HIV-infected persons. Those exposed through IDU in particular are likely to be at higher risk of mortality than the general population regardless of HIV infection, and we have presented our estimates of the cumulative excess mortality proportion excluding this group. Nonetheless, our results are interpretable as estimates of the excess mortality among HIV-infected individuals, who may differ from a general population not only in being infected with HIV but also in other factors.”

    To echo Prof. Bauer’s oft-expressed sentiment: “I’m speechless”. The authors spell out in detail the most classic of all reasons why a study is invalid: like has not been compared with like. But instead of expressing regret, they suggest with completely straight face that this utterly devastating shortcoming, which should immediately have disqualified the study for funding, is a good thing, since it allows us freedom of interpretation, which in this case is to be used to blame lifestyle rather than HAART for any excess excess (repetition intended) mortality. Nudge, nudge; wink, wink.

    But before the authors arrive at the lifestyle explain-all, they have ample opportunity to demonstrate their ingenuity:

    1) The authors would like to correlate the increase in “uptake of HAART” with the decrease in excess mortality. Unfortunately, mortality continued decreasing even after uptake of HAART leveled off. But the authors don’t even flinch; with a single glance in their crystal ball they credit NNRTI-based HAART and ritonavir “boosters” with the continued positive trend.

    “Our more recent data show that reductions have continued to 2004-2006, with excess mortality in this period 94% lower than pre-1996 levels. Corresponding to these reductions, the uptake of HAART increased, and though this leveled off after 2001, there followed an increasing use of NNRTI-based HAART as the first-line treatment regimen and a substantial increase in the boosting of PI-based regimens.”

    The fact that they’ve just told us that the median time from seroconversion to starting HAART has INCREASED during the time of positive development does not even enter into the equation; neither does it prevent Dr. Porter from recommending that treatment should start earlier, as we saw previously.

    “The median time from HIV seroconversion to starting HAART was 1.6 (IQR, 0.7-3.5) years in 1996-1997 and 1.4 (IQR, 0.6-3.4), 1.8 (IQR, 0.7-5.6), 2.4 (IQR, 0.8-6.7), and 2.2 (IQR, 1.0-4.8 ) years in 1998-1999, 2000-2001, 2002-2003, and 2004-2006, respectively”.

    2) The authors were not able to establish a straightforward correlation between uptake of HAART and decrease in excess mortality. However, they WERE able to establish a straightforward correlation between better drug adherence and higher mortality:

    “We found that older age was highly predictive of excess mortality prior to 1996, and this effect broadly continued in later calendar periods, despite suggestions in the literature that increasing age is associated with better adherence to HAART.”

    In other words, those who rarely miss a pill are at highest risk of dying. But the authors are as dismayed by the recalcitrance of their statistics as Banquo and Macbeth by the entrance of the Norweyan lord into battle:

    “Some studies have found that older individuals experience slower immune recovery following HAART initiation, which could reflect the state of thymic function and may in part account for their continuing excess risk of death”

    The authors are so pleased with this purely speculative partial account for a major challenge to their basic premise that they don’t even feel the need to explain why the slower immune recovery would be significant since the excess mortality is measured against people with supposedly equally slow immune recovery. Neither does it trouble the authors that the older people are, the less likely they are to lead the extreme lifestyles that was supposed to be the best explanation for excess excess (repetition intended) mortality.

    No doubt this study will go up on as an example of the rigor of HIV science.

  5. Yes, you’re right, MacD, the major flaw in this paper is that all the years before 1996 are lumped together into so-called “pre-HAART”, neglecting to consider the enormous demographic and clinical changes in “AIDS” and nucleoside analogue therapies in the 15 or so years from 1981 when the first cases were reported to 1996 when HAART hit market.

    For more on this specific type of statistical trickery, see

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