Peer Reviewing Peter Duesberg – REJECTED—RETRACTED—REJECTED Again

This summer’s saga of Peter Duesberg’s Medical Hypotheses retracted article should probably be put to rest. The sad story of this broken scientist has been told many times. Here though Duesberg reaches an all time low as he teams up with pseudoscientist Henry Bauer to yet again claim that HIV is harmless.

Duesberg and his long time accomplice David Rasnick along with Loch Ness Monster Scholar Henry Bauer published the article “HIV-AIDS hypothesis out of touch with South African AIDS – A new perspective” in the non-peer reviewed journal Medical Hypotheses. The article focused on the South African AIDS epidemic and research reported by Harvard scientist Dr. Pride Chigwedere in the respected Journal of AIDS. Duesberg disputes the death of over 300,000 South Africans and 30,000 babies unnecessary infected with HIV. Duesberg and Rasnick have a stake in denying AIDS in South Africa because they advised former President Thabo Mbeki to deny AIDS and delay HIV treatments. Duesberg’s ideas were so flawed that the publisher, Elsevier Science, took the unusual step of retracting the article.



The authors first tried to publish the article in the Journal of AIDS as a commentary on the Harvard study. But Duesberg was rejected after peer review. Of course Duesberg accuses the review process of corruption and unfairness. The authors said the following, “A precursor of this paper was rejected by the Journal of AIDS, which published the Chigwedere et al. article, with political and ad hominem arguments but without offering even one reference for an incorrect number or statement of our paper (available on request).”

Not surprisingly, requests for the reviewer comments are not honored; leaving us to imagine what the peer reviewers said about Duesberg's article. I decided to undertake a simulated peer review of the Duesberg article.
As the Editor in Chief of a peer reviewed journal, I figured, why not?

I took several steps to perform as close to a true peer review as possible. I stripped the text of all identifying information – the authors' names were removed from the paper. The text, tables and figures were cut and pasted to create a double spaced manuscript document suitable for blind review. I asked three leading researchers with expertise in South African AIDS to review the paper. None of the reviewers had any interest in AIDS denialism and none was aware of the Duesberg article. Here are my instructions:

"The attached manuscript is not under consideration at the journal which I edit, AIDS and Behavior. The paper is a critique of a modeling study of AIDS in Africa. This critique is a real manuscript and I am seeking peer reviews. Once you complete the task, I will inform you of what this is all about. I am asking that you, (1) Review the paper as if it were submitted to a journal of the caliber of Journal of AIDS or an equal level public health journal. (2) Provide written comments for the authors (no more than 1 single spaced page). (3) Recommend a decision to reject outright, reject with the option to resubmit, or accept the paper.”

All three reviewers recommended rejection. The simulated reviews offer a glimpse of what may have been raised by the Journal of AIDS. The consistency of our three independent reviews is remarkable.

Medical Hypotheses would probably have rejected the paper if only they sent it out for peer review.

Why Peter Duesberg continues to humiliate himself by ignoring science and affiliating with pseudoscientists remains a mystery.

The unedited blind reviews follow.

Review #1

This paper is an attempt to rebut a recently-published estimation of the lost benefits of antiretroviral therapy (ART) use in South Africa. The original paper essentially argued that by failing to implement an ART program that was “reasonably feasible” at the time, the South African government failed to prevent 330,000 deaths and 2.2 million person-years. The authors of the current article believe that the estimate is overblown and unrealistic; furthermore they argue that HIV does not cause AIDS. For the latter argument, apart from a very few scientists who believe HIV does not cause AIDS, there is broad scientific agreement and decades of scientific evidence that contradicts this claim of the authors. I cannot see why JAIDS would want to (re) engage in this obviously dead-end debate.

In addition, the paper has a number of methodological flaws, as noted below. I would therefore recommend rejection.

Major comments:
You fault Chigwedere and colleagues for overestimating the number of deaths averted, but the data that you use to revise (downward) his estimate is obviously wrong. Who but an AIDS denialist would believe that a) the South African mortality registration system would yield an accurate count of deaths due to HIV/AIDS and b) that 1 death per 1000 HIV-positive people per year were anything close to an accurate measure of the rate at which people with HIV/AIDS die. Even a back of the envelope calculation is enough to show that this estimate is off by several orders of magnitude: If the average person, untreated, with HIV/AIDS in South Africa lives 10 years as has been roughly shown in several other African natural history studies, then on average (assuming constant rates of infection) about 10% will die per year. This number is clearly much closer to the truth and 1 death per 1000 HIV-positive person per year is obviously wildly off target. In short, mortality registration is a very poor and inaccurate measure of HIV/AIDS deaths and cannot and should not be trusted to estimate how many people with HIV are likely to die per year.

You make much of the fact that the population in South Africa actually increased during the time period under consideration, but fail to realize that population can increase even in the face of large number of HIV/AIDS deaths; these two things are not mutually exclusive as you imply. The question is not whether the population increased – you can still have an increasing number of deaths accompanied by and increased size of the total population if there are more births or more immigration. Rather, the question is whether deaths from HIV/AIDS increased and how many could have been averted if treatment had started earlier than it did. Further, you state that “since the African HIV-epidemics coincided with steady and massive growths if the affected populations, we conclude that HIV-epidemics are not likely causes of AIDS epidemics.” In light of the above, this makes no sense at all. The assertion that because there has been population growth HIV epidemics do not likely cause AIDS epidemics is illogical and unscientific.

You seem to miss the point about vertical transmission, either unwittingly or purposely. When it comes to estimating the rates of vertical transmission, you fail to acknowledge that several randomized clinical trials (RCTs) have shown definitively the positive impact of ART in reducing the probability of vertical transmission. In other words, it is well established that antiretroviral drugs can help prevent a significant amount of vertical transmission, a fact you prefer to ignore.

You mix up population prevalence and antenatal prevalence, which, importantly, measure 2 different things. These things cannot be used interchangeably. Your table 1, 2nd column is “HIV in the South African population” yet the data you display there are the national antenatal statistics, very different indeed from the population prevalence that is implied. The same is true of your 2nd paragraph on page 6.

You further mix up prevalence and incidence, again, basic epidemiological concepts. Page 20, graph b is NOT HIV incidence as labeled at the bottom of that page, but rather annual antenatal prevalence.

You imply that toxicity (in the context of vertical transmission) is universal to all who use ARVs. You fail to mention or quantify the frequency of these events; nor do you meaningfully weigh the pros and cons of receiving ART and avoiding an HIV infection compared to the likelihood of a severe and debilitating side effect. Every drug has side effects and can therefore be toxic. The question is whether the benefits outweigh the risks, something that you ignore by repeatedly raising the “toxicity” alarm without quantifying its frequency or severity. Asprin has side effects and taken at extreme doses can cause toxicity. But that does not mean you shouldn’t use asprin when you have a headache.

Reviewer #2

I think we are long past the issue of whether HIV causes AIDS. I think it is very important to be open to other ideas including controversial ones. But even this primary issue is not taken on in a very convincing manner.

The basic argument is that if HIV is really responsible for so many deaths, why aren't they reflected in the death rates. I'm not a demographer, but the demographic projections I have seen for almost all of the hyperendemic countries still allow for substantial population growth even with AIDS.

South Africa is a country where there is a lot of denial and silence about when and whether someone dies of AIDS, so it would not be surprising to see a lot of underreporting in official cause of death. So the 1 per 1000 reported HIV-death rate (or even 2.5%) is not at all credible.

The rates of HIV prevalence are grossly overstated (given as 25-30%). Actually the overall rate for the population over 2 in South Africa in 2008 in the HSRC survey was only 10.9%. So the author's HIV-attributable mortality is widely off the mark.

As I look at the numbers, it is not unreasonable that a country such as South Africa could be growing at about 600,000 per year while at the same time experiencing 66,000 excess deaths per year from HIV/AIDS.

The authors do make a valid point that we may be underestimating the long-term toxicity of ARVs.

But I do not see value over all in this paper and would not recommend if for publication (i.e. reject outright.)

Reviewer #3

This manuscript responds to a recent study that found that in South Africa, at least 3.8 million person-years were lost due to delays in implementing ARV/prevention of mother to child transmission (PMTCT) programs because of beliefs that HIV was not the cause of AIDS and that ARV were not useful to patients (Chigwedere). The manuscript raises two issues: (1) What evidence exists for the huge loss of lives? And (2) What is the evidence that anyone would have benefited from the ARVs? The manuscript also raises the question as to whether HIV is a passenger virus.

Overall, the manuscript does not provide a convincing or logical argument to counter the assumptions made by the Chigwedere study. For instance, while the manuscript provides some evidence for their hypotheses, the authors do not address some of the claims of the Chigwedere article. For instance, the burden is on the authors to counter Chigwedere’s statement that “HIV satisfies all of Koch’s postulates…and all of…Hill’s epidemiological guidelines for assessing causality.” I would recommend rejecting the manuscript for publication based on its lack of logic in its arguments against the Chigwedere study, but also in the presentation of the authors’ own hypothesis.

In the first section of the manuscript, the authors state that there is no evidence of huge losses of life. The data are presented along with the assumption that population growth could not have occurred concurrently with an HIV epidemic. This assumption does not demonstrate knowledge of basic population dynamics or demography (e.g. a population can grow as long as birth rates are higher than death rates). The authors seem to conclude that HIV-related death and population growth are mutually exclusive, which is not true.

The authors point to data that only 2.5% of total registered mortality were due to HIV-deaths.

The authors do not address (1) issues of quality of these data, and more importantly (2) the attributable fraction of mortality resulting from HIV-related deaths. The counter-factual of how many deaths from TB, for instance, would have been avoided if HIV had been reduced is not considered.

Page 9 – the authors assume that all pathogenic viruses “act” the same in a given population. What is the basis of this assumption? Are there exceptions to this (e.g. other viral STIs?)

In the second section of the manuscript, the authors state that there are unresolved problems with the belief that AZT/Nevirapine inhibit HIV. The authors do not address the evidence (notably those cited by Chigwedere) that indicate (using “gold-standard” epidemiological studies) that AZT/ZDV are effective.

On pages 10-11, the authors point out some of the negative outcomes resulting from ART and PMTCT. However, the authors do not indicate how common these outcomes are and whether the burden of these outcomes are greater than the burden associated with HIV infection. The authors then make a conclusion that the negative impacts of treatment means that they do not have any benefit, which is not a logical conclusion.