Tag Archives: antiretroviral therapy

To Resign over an Editorial Decision You Disagree With

What would you do if you were serving on the editorial board of a scientific journal which had just published a manuscript that you knew was seriously flawed. Moreover, you knew that publication of the manuscript might seriously undermine global public health? That was the circumstance of cell biologist Klaudia Brix, Professor of Cell Biology, Jacobs University Bremen, Germany, when, in 2011, the Italian Journal of Anatomy and Embryology (IJAE)—the official publication of the Italian Society of Anatomy and Histology—published a paper by infamous AIDS denialist, Peter Duesberg, which reiterated his already discredited argument that HIV (the human immunodeficiency virus) does not cause AIDS (1). Brix resigned in protest from the IJAE editorial board. But why is that noteworthy? Remarkably, she was, for a time, the only member of the journal’s 13-person editorial board to do so, despite other members having similar misgivings over the decision to publish the paper. Afterwards, Heather Young, an anatomy and neuroscience researcher at the University of Melbourne, likewise resigned from the IJAE editorial board. Here is the background to this state of affairs.

Peter Duesberg is not the only AIDS denialist. However, he has been the most infamous of the AIDS denialists. HIV is a retrovirus, and Duesberg is the only AIDS denialist who also happens to be an expert retrovirologist. In fact, Duesburg was at one time a highly esteemed retrovirologist. In 1985 he was elected to the U.S. National Academy of Sciences; mainly for his 1970 discovery, with Peter Vogt, of the first known retroviral oncogene—the Rous sarcoma virus v-src.

AIDS denialist, Peter Duesberg
AIDS denialist, Peter Duesberg

Duesberg first put forward his denialist view in a 1987 paper in Cancer Research (2), which asserted that AIDS results from drug abuse, parasitic infections, malnutrition, and antiretroviral drugs. In Duesberg’s assessment, HIV is just another opportunistic infection. He has maintained that view since then, despite overwhelming evidence to the contrary. Consequently, he is looked upon as a pariah by the scientific community.

Even though Duesberg’s denialist views have been rejected by AIDS experts, Duesberg’s standing as a retrovirologist enabled him to yet influence some public health officials. In 2000, Duesberg was serving on a panel advising Thabo Mbeki (President of South Africa after Nelson Mandela) on how to manage the South African AIDS outbreak. Although Mbeki was an able and intelligent leader, he accepted Duesberg’s denialist view that HIV was not the cause of the South African AIDS epidemic. Thus, Mbeki allowed the South African outbreak to get completely out of control (3). Two independent studies later concluded that over 300,000 South African AIDS deaths would not have occurred if the Mbeki government’s public health policy had not followed the denialist view. Many thousands of South African AIDS victims, including infants, would have been spared infection if the government had publicized that AIDS is an infectious disease, and if it had made antiretroviral drugs available, particularly to pregnant women (1).  See Asides 1 and 2.

[Aside 1: The reasons why Mbeki assented to Duesberg’s denialist view are not clear. One possibility is that Mbeki held strong anti-colonialist and anti-West sentiments—born of having come of age during South Africa’s apartheid era—which led him to see his country’s AIDS crisis as a means by which the West sought to exploit his nation. To that point, he may have doubted the efficacy of expensive antiretroviral drugs, which were available only from large Western pharmaceutical companies. Moreover, the cost of treating the 5 million or more HIV-infected South Africans with those drugs would have exceeded the annual health department budget of his poverty-stricken nation by a factor of ten. Mbeki did accept that AIDS is the consequence of a breakdown of the immune system. But he was inclined to believe (or at least claimed) that poverty, bad nourishment, and ill health, rather than a virus, led that breakdown; a stance that enabled him to justify treating poverty in general, rather than AIDS in particular. Duesberg defended Mbeki in his publications, denying that hundreds of thousands of lives were lost in South Africa because of the unavailability of anti-retroviral drugs. But in 2002, after Mbeki suffered political fallout from the consequences of having acceded to Duesberg’s views, he tried to distance himself from the AIDS denialists, and asked that they stop associating his name with theirs.]

[Aside 2: The 2000 International AIDS Conference was taking place in Durban (a city in the South African province of KwaZulu-Natal) at the same time that Mbeki’s AIDS panel was convening in Johannesburg. Consequently, the denialist views expressed by Mbeki’s panel were also being heard in Durban. This prompted the so-called “Durban Declaration,” signed by over 5,000 scientists and physicians, and published in Nature, which proclaimed that the evidence that HIV causes AIDS is “clear-cut, exhaustive and unambiguous”.]

Well before Duesberg submitted his paper to IJAE, the arguments put forward in the paper had already been appraised and rebuffed by the scientific community. Indeed, the paper had previously been rejected by several other journals. The first submission was to the Journal of Acquired Immune Deficiency Syndromes (JAIDS), a peer-reviewed medical journal covering all aspects of HIV/AIDS. The JAIDS editors found that Duesberg’s contentions in the paper were based on a selective reading of the scientific literature, in which he dismissed all the vast evidence that HIV is the etiologic agent of AIDS. Not surprisingly, JAIDS rejected the paper, with one peer reviewer even warning that Duesberg and co-authors could face criminal charges if the paper were published.

After JAIDS rejected the paper, Duesberg  submitted a revised version to Medical Hypotheses (4). Like the original paper sent to JAIDS (as well as the version accepted by IJAE), the paper submitted to Medical Hypotheses contained data cherry-picked to cast doubt on HIV as the cause of AIDS. Nonetheless, Medical Hypotheses accepted the paper. However, the paper never went to press. But first, what was the explanation for the seemingly bizarre decision to accept the paper?

The answer laid in the fact that Medical Hypotheses was the only journal of its parent publisher, Elsevier, that did not use peer review; instead relying on its editorial board to select papers for publication. In any case, before the accepted paper went to press, prominent AIDS researchers, including Nobel laureate Francoise Barre-Sinoussi (co-discoverer that HIV is the cause of AIDS, 5), complained to Elsevier that the paper would have a negative impact on global healthcare, and requested that the paper be withdrawn.

Elsevier responded to these protests by asking the editors of another of its journals, The Lancet, to oversee a peer review of the paper. The Lancet editor sent the paper to five external reviewers, each of whom found that it contained numerous errors and misinterpretations, and that it could threaten global public health if it were published. Elsevier then permanently withdrew the paper.  Elsevier also instituted a peer-review policy at Medical Hypotheses (and fired the journal’s editor, who resisted the change).

The Medical Hypotheses incident resulted in more notoriety for Duesberg when the University of California, Berkley, where Duesberg is still a professor of molecular and cell biology, bought charges of misconduct against him for making false scientific claims in the paper, and for a conflict-of-interest issue. Apropos the latter, Duesberg did not reveal that co-author David Rasnick had earlier worked for Matthias Rath, a German doctor and vitamin entrepreneur, who sold vitamin pills as a therapy for AIDS. Duesberg was later cleared of both charges. But the next iteration of paper, to IJAE, did not respond to these allegations.

Duesberg regarded Elsevier’s actions as another example of “censorship” imposed by the “AIDS establishment.” Undeterred however, he submitted a revision of the paper to IJAE, which that journal then accepted, prompting Klaudia Brix and Heather Young to resign from that journal’s editorial board. The IJAE paper contained the same cherry-picked data and discredited assertions that were rejected earlier by JAIDS and Elsevier.  Moreover, publication of the paper still posed a threat to global public health. What then was behind the IJAE decision to publish?

Here is what happened. The paper was “peer-reviewed” by IJAE, but by only two reviewers; one of whom was Paolo Romagnoli, the IAJE editor-in-chief, who is neither a virologist or an epidemiologist but, instead, a cell anatomist. Consequently, the paper underwent only one external review, and there is no information regarding whether the lone external reviewer was an AIDS expert. One board member (who did not resign) later commented: “Only one [external] reviewer in my mind is not enough for manuscripts of a sensitive nature… (6)” [But this comment too is a bit troubling. Bearing in mind that the paper contained numerous errors and misinterpretations, would those have been okay if the paper were not of a “sensitive nature”?]

One also might ask why a journal that specialized in anatomy and embryology would consider a paper about the cause of AIDS. To that point; Klaudia Beix gave, as a reason for her resignation from the IJAE board, her belief that a journal should function within its scientific “scope” (6). So how did Romagnoli, the IJAE editor-in-chief, justify his decision to consider the paper?  He did so by asserting that it dealt with “issues related to the biology of pregnancy and prenatal development and with the tissues of the immune system (6).” But despite Romagnoli’s contention, the only mention of embryology in the paper was a short comment in the abstract: “We like to draw the attention of scientists, who work in basic and clinical medical fields, including embryologists, to the need of rethinking the risk-and-benefit balance of antiretroviral drugs for pregnant women, and newborn babies (1).”

As for Romagnoli’s reliance on only two reviewers, he justified that stance on the fact that the reviewers had concurring opinions. Moreover, he claimed that his criteria for selecting reviewers—apparently irrespective of their expertise—was to choose individuals (himself included) who he believed would not reject a paper merely because it challenged prevailing opinion.

But is there any possibility that Duesberg might be right? The answer is virtually none whatsoever. An earlier post noted: “…the evidence that HIV causes AIDS is, without exaggeration, overwhelming. Consider just the following. Data from matched groups of homosexual men and hemophiliacs show that only those who are infected with HIV ever develop AIDS. Moreover, in every known instance where an AIDS patient was examined for HIV infection, there was evidence for the presence of the virus. These data have been available for years, and Duesberg should have been aware of them. What is more, there has been the enormous success of antiretroviral therapy in changing AIDS from a nearly invariably fatal disease, into a manageable one, for many HIV-infected individuals (3).”

Even so, Duesberg is not regarded as a pariah by AIDS experts merely because his views concerning the connection between HIV and AIDS challenge accepted wisdom.  Instead, as asserted by Harvard University AIDS epidemiologist, Max Essex, Duesberg has sustained a “dangerous track of distraction that has persuaded some people to avoid treatment or prevention of HIV infection (6)”.

A scientist mounting a long-time challenge to the “establishment,” and being ridiculed for his views, before eventually being vindicated, makes for a very good story. However, such instances are very rare. Exceptions include Howard Temin (7) who hypothesized reverse transcription, and Stanley Pruisner (8) who hypothesized prions—infectious agents that contain no nucleic acid genome. Both researchers had to endure widespread ridicule for several years. But, and importantly, irrefutable evidence eventually accumulated to support their hypotheses. And, finally, both were awarded Nobel Prizes. But Duesberg has not been vindicated and, almost certainly, he  never will be.

References:

1. Duesberg PH, et al., 2011. AIDS since 1984: no evidence for a new, viral epidemic – not even in Africa. Italian Journal of Anatatomy and Embryololgy 116:73–92. http://fupress.net/index.php/ijae/article/view/10336/9525

2. Duesberg P, 1987. Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res. 47:1199–220. PMID3028606.

3. Thabo Mbeki and the South African AIDS Epidemic, Posted on the blog July 3, 2014.

4. Duesberg PH, et al., 2009. WITHDRAWN: HIV-AIDS hypothesis out of touch with South African AIDS – A new perspective. Medical Hypotheses. doi:10.1016/j.mehy.2009.06.024. PMID19619953.

5. Who Discovered HIV, Posted on the blog, January 24, 2014.

6.  Corbyn Z. 2012. Paper denying HIV–AIDS link sparks resignation: Member of editorial board quits as editor defends publication. Nature doi:10.1038/nature.2012.9926.

7. Howard Temin: “In from the Cold, Posted on the blog December 14, 2013.

8. Stanley Pruisner and the Discovery of Prions: Infectious Agents Comprised Entirely of Protein, Posted on the blog December 15, 2016.

 

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Thabo Mbeki and the South African AIDS Epidemic

I recently watched the fact-based 2009 movie Endgame, which depicts the final days of apartheid in South Africa. The movie focused on how a young Thabo Mbeki facilitated the late 1980s secret talks between Afrikaner leaders and the about-to-be freed Nelson Mandela’s African National Congress. The purpose of these talks was to arrange negotiations between de Klerk’s apartheid government and the ANC, in order to facilitate the stable transition of South Africa from apartheid.

imbeki, mandelaThabo Mbeki with Nelson Mandela

Mbeki is portrayed in the film as a wise, compassionate, and respected political activist. Moreover, all commentary on the movie that I’ve read is consistent with it having accurately depicted people and events. Here then is Mbeki in a different guise, when dealing with the South African AIDS epidemic, after succeeding Mandela as the nation’s president. As usual, we begin with some background.

The South African AIDS outbreak may well have been the most devastating of all the world’s AIDS epidemics. Consider the following statistics. By 2007, more than one in five South African adults (approximately 5 million people) were living with HIV, and the disease claimed nearly 1,000 lives daily. Shockingly, 71% of all deaths among individuals between 15 and 49 years of age were due to AIDS. Moreover, a 15-year old South African had a 50:50 chance of dying of AIDS before his or her 30th birthday.

Yet despite these statistics, South Africa escaped the initial HIV/AIDS epidemic of the 1980’s. Why then did HIV/AIDS get so out of hand in South Africa in the early 21st century? One reason is that it was a time when the government was preoccupied with the nation’s poverty and its transition from apartheid. Moreover, and importantly, any rational efforts to deal with the South African HIV/AIDS epidemic were severely compromised when, in 2001, President Mbeki embraced the “denialist” view that AIDS is not caused by HIV. [See the addendum on the AIDS denialists at the end of this posting.]

Mbeki’s “denialist” position on AIDS dates back to 2001, when his minister of health convened a 36-member international panel of supposed AIDS experts to advise Mbeki on how best to confront the nation’s AIDS crisis. Regrettably, the14 known HIV/AIDS denialists, who were invited by the health minister to join Mbeki’s AIDS Advisory Panel, convinced Mbeki to adopt their denialist point of view.

Afterwards, Mbeki and his administration were repeatedly accused of improperly dealing with their nation’s AIDS epidemic. Noting that AIDS patients succumb to the opportunistic infections that appear following the HIV-caused breakdown of their immune systems, South African AIDS patients, who used the public health system, were able to get treatment for their opportunistic infections. However, the Mbeki government prevented those patients from receiving antiretroviral therapy, which might have prevented the breakdown of their immune systems in the first place.

Governmental restrictions against the use of antiretroviral drugs remained in place until August 2003, when the South African Cabinet overruled Mbeki, and declared as Cabinet policy that HIV is the cause of AIDS. Moreover, the cabinet promised to formulate a national treatment plan that would include antiretroviral therapy. Yet despite the efforts of the cabinet to make antiretroviral drugs the mainstay of the country’s treatment plan, the health minister continued to promote nutritional approaches to treating AIDS, while also proclaiming the toxicity of the antiretroviral drugs.

The continued unwillingness of the Mbeki administration, to acknowledge that HIV is the cause of AIDS, prevented the cabinet’s more enlightened AIDS policy from being fully realized. By the end of 2007, only about 28% of South Africa’s AIDS patients were able to obtain antiretroviral therapy. And, since many HIV-infected pregnant women were not getting the antiretroviral drugs that might have prevented transmission of the virus to their babies, HIV remained tragically common among South African children. In this regard, in 2007, UNAIDS reported that there were about 280,000 children under 15 years of age who were living with HIV in South Africa. Moreover, AIDS-related adult deaths resulted in 1.4 million South African children becoming orphans in 2007; a rise from the 780,000 new orphans reported in 2003.

A 2008 report from the Harvard School of Public Health estimated that Mbeki’s denialist stance caused an estimated 330,000 or more preventable AIDS-related deaths in South Africa. That estimate was based on comparing the effect of antiretroviral therapy in neighboring Botswana and Namibia, to the state of affairs in South Africa, during the period from 2000 to 2005.

Mbeki resigned the presidency in September 2008, after losing the support of his party. His resignation was not related to his AIDS denialism. Rather, it involved his alleged interfering with the country’s National Prosecuting Authority in a political matter.

Following Mbeki’s resignation, his successor, Kgalema Motlanthe, fired health minister Manto Tshabalala-Msimang, who, like Mbeki, was an AIDS denialist. South Africa then initiated the largest antiretroviral therapy roll-out program in the world, resulting in a 5-year jump in life expectancy to a current 36 years-of age. Moreover, in 2011, there were 100,000 fewer AIDS-related deaths in South Africa than occurred in 2001, and over 300,000 fewer than occurred in 2006. Still, about 5.6 million South Africans were estimated to be infected with HIV in 2011; the highest number of infected people in any country! Almost one-in-three women aged 25-29, and over a quarter of men aged 30-34, were HIV-positive

Considering the prevalence of HIV in South Africa, it may surprise some readers that there is widespread prejudice in the country against those living with AIDS. With that in mind, we note Nelson Mandela’s action when his son died of AIDS in 2005. Mandela deliberately revealed the cause of his son’s death to the public. His purpose was to countermand the stigma associated with being infected with HIV and, also, as a “political statement designed to… force the President [Mbeki] out of his denial.” Earlier, in 2002, South African politicians, who were loyal to Mbeki, attacked Mandela for questioning the government’s AIDS policy.

Bearing in mind that Mbeki was a respected and intelligent leader, how might we explain his rejection of the orthodox view, based on indisputable evidence, that HIV is the cause of AIDS? Could he simply have been taken in by the AIDS denialists? Or, might there be more? A likely possibility is as follows. Mbeki was known to harbor strong anti-colonialist and anti-West sentiments, born of having come of age during South Africa’s apartheid era. Perhaps his earlier experiences caused him to see his country’s AIDS crisis as a means by which the West sought to exploit his nation’s people.

In the same vein, Mbeki was acutely conscious of South Africa’s poverty and, consequently, was likely affected by the huge expense of antiretroviral drugs. In that regard, his health minister advised him that the cost of treating the 5 million or so HIV-infected South Africans with AZT would exceed the annual health department budget by a factor of ten. And, given Mbeki’s anti-West sentiments, he was particularly sensitive to the fact that antiretroviral drugs were made and sold by powerful Western pharmaceutical companies. Additionally, Mbeki may have been skeptical of the efficacy of those drugs; an attitude reflecting the fact that the health policies of the colonial and apartheid governments in South Africa indeed were often self-serving and manipulative.

Mbeki indeed accepted that AIDS results from the collapse of the immune system. Nevertheless, he believed (or at least claimed) that the cause of that collapse was poor nutrition and poor health resulting from poverty, rather than from a virus. Thus, he argued that he needed to attend to poverty in general, rather than to AIDS in particular.

Treating HIV/AIDS has indeed been expensive for South Africa. Additionally, the more than $1 billion that the nation now spends annually on its HIV/AIDS program has been largely financed from its own domestic resources. Yet, South Africa is still desperately trying to emerge from the poverty of its former oppression. So, if you were in Mbeki’s position as the President in 2001, would you have chosen to support AIDS therapy, which might have exceeded the limits of your financial resources for the foreseeable future or, instead, would you invest in water systems, housing, schools, and hospitals? And what of other crucial social and medical problems that still abound in South Africa, such as malaria, tuberculosis, and violence against women? You cannot have it all. And even if Mbeki and his government had believed in and fully supported antiretroviral therapy, impediments to its effectiveness would still have remained. These comment are not meant to defend Mbeki, but, instead, to point up the complexity of the AIDS problem in a poverty-stricken nation emerging from apartheid.

Addendum: The AIDS denialsts: While some AIDS denialists had legitimate scientific credentials, none, except Peter Duesberg, was an expert retrovirologist. Indeed, before Duesberg emerged as an AIDS denialist, he made important contributions to the retrovirus field, including his finding that Rous sarcoma virus contains an oncogene (1). For this contribution, and others, Duesberg was elected to the prestigious U.S. National Academy of Sciences. However, once Duesberg broke ranks with other scientists over AIDS, he became a scientific outcast, no longer receiving invitations to scientific conferences and no longer able to obtain research grants.

Duesberg advocated the belief that AIDS results from drug abuse, parasitic infections, and malnutrition, rather than from a retrovirus, and that HIV itself is just another opportunistic infection. He stated that if he discovered that he was HIV antibody-positive, he would take that as an encouraging sign that his immune system was working.

Yet Duesberg was never able to offer any plausible evidence that might substantiate his dissident views. Moreover, he repeatedly ignored the numerous rebuttals of his claims that appeared in the scientific literature. [Kary Mullis, who was awarded the Nobel Prize for inventing the polymerase chain reaction (PCR), is another AIDS denialist with legitimate, indeed prestigious scientific credentials. But, unlike Duesberg, Mullis has no expertise that might be relevant to HIV/AIDS.]

In an interesting aside, in 2009, Duesberg published a paper in Medical Hypotheses, which defended Mbeki and disputed the 2008 study which reported that hundreds of thousands of lives were lost in South Africa because antiretroviral drugs were not available to AIDS patients there. Prominent AIDS researchers, including Nobel laureate Francoise Barre-Sinoussi (2) then complained to the journal’s publisher, Elsevier, asking that the paper (which had not yet been printed) be withdrawn.

Since Medical Hypotheses was the only Elsevier journal to have a policy against peer review, Elsevier then asked the editors of another of its journals, The Lancet, to oversee review of Duesberg’s paper. After The Lancet reviewers found that the paper contained numerous errors and misinterpretations, Elsevier permanently withdrew it. What’s more, Elsevier then forced Medical Hypotheses to introduce peer review. [On the one hand, the editorial policy of Medical Hypotheses, to “consider radical, speculative and non-mainstream scientific ideas,” may well have provided a means for airing new, potentially important premises. On the other hand, publication of Duesberg’s denialist notions, in what is nominally a scientific journal, would have given those notions an air of credibility, potentially impairing worldwide efforts against AIDS.]

Far from conceding his position, Duesberg claimed that Elsevier’s measures are the latest example of “censorship” imposed by the “AIDS establishment.” He then published a revised version of the paper in the Italian Journal of Anatomy and Embryology, causing further controversy.

So, taking into account Duesberg’s very real expertise as a retrovirologist, can he possibly have been right about HIV and AIDS, and is his alternative view helpful in the fight against the disease? It would make for a fascinating story if the answers were yes, or just even maybe. But, the evidence that HIV causes AIDS is, without exaggeration, overwhelming. Consider just the following. Data from matched groups of homosexual men and hemophiliacs show that only those who are infected with HIV ever develop AIDS. Moreover, in every known instance where an AIDS patient was examined for HIV infection, there was evidence for the presence of the virus. These data have been available for years, and Duesberg should have been well aware of them. What is more, there has been the enormous success of antiretroviral therapy in changing AIDS from a nearly invariably fatal disease, into a manageable one, for many HIV-infected individuals.

It is not known how many people might have been infected with HIV, or might not have benefited from effective antiretroviral therapy, because they heeded the arguments of the AIDS denialists. These individuals continue to tout their notions, to the detriment of the millions of HIV-infected individuals who listen to them.

1. The relevance of retroviral oncogenes is discussed in: The Politics of Science: Vignettes Featuring Nobel Laureate Harold Varmus during his Tenure as Director of the NIH, posted on the blog, June 2, 2014.

2. see: Who Discovered HIV, posted on the blog, January 24, 2014