TRACKING DRUG RESISTANCE IN SOUTH AFRICA Andrew McIntyre on Thabo Mbeki’s determination to buck conventional wisdom on AIDS

By Andrew McIntyre

The Australian Financial Review 31 March 2000

In late October last year, South African President Thabo Mbeki, under pressure to supply the anti-AIDS drug AZT to thousands of rape victims in the country, let off a bombshell by strongly criticising the drug and declaring in Parliament that there exists a large volume of scientific literature alleging, among other things, the toxicity of this drug is such that it is in fact a danger to health".

While the news was briefly reported in Australia and elsewhere, the extent of the reaction and the furious debate that has followed in South Africa, has largely escaped international attention.

Mbeki claimed that AZT was being challenged by court cases in the US, Britain and South Africa and asked for an official inquiry into the issue by the Minister for Health, Dr Manto Tshabalala-Msimang.

His announcement produced bafflement and intense anger amongst health professionals who maintain that AZT is safe and believe Mbeki has political motives. The drug’s manufacturer, Glaxo-Wellcome, responded that it was unaware of any such lawsuits. AZT is the mainstay of international efforts to treat AIDS patients and to prevent the transfer of the virus from HIV positive mothers to their babies.

Dr Joseph Perriens, the head of the care and support division of the UN AIDS program in Geneva, suggested Mbeki "inform himself better... [and] recast the debate in terms of cost". Dr Salim Abdool Karim, the head of AIDS research at the Medical Research Council, said, "I think [that] if the President doesn’t want to provide AZT, he should find an excuse based on fact."

The South Africa Government has come under increasing pressure to provide expensive Western drugs like AZT that it cannot afford. There has been a bitter dispute over the rules which protect worldwide patents of pharmaceuticals. However, Mbeki’s questioning of the drug was initially sparked by an Australian research group in Perth, headed by Eleni Papadoupoulos, which claims its work shows that AZT is, pharmacologically, a failure.

The drug manufacturers and clinical AIDS specialists claim that the drug improves "quality of life" and can reduce transmission of HIV. But Mbeki’s statement has added momentum to critics of AZT who argues that the cure might just be worse than the disease. There is a growing number of scientists and medical professionals claiming that not only is there no clear scientific proof that AZT kills HIV or cures AIDS, but that there is ample evidence that it kills humans.

As evidence, they cite the 1994 publication of results from the Concorde trial, the most thorough double-blind randomised comparison of two policies of AZT treatment. This involved 1,749 symptom-free, HIV-infected individuals from centres in the UK, Ireland and France. The 347 deaths during the trial outnumbered the total of those in all other published trials in symptom-free and early symptomatic infection. The results showed there was no statistically significant difference in clinical outcome between the two therapeutic policies. In 1995, extended results of the Concorde study showed a significant increased risk of death among those patients treated early. However, despite this evidence that patients treated with AZT may continue to develop AIDS diseases, that the side-effects of AZT may mimic AIDS and that AZT given to non-HIV-infected babies causes the AIDS-defining pneumonia PCP, AZT continues to be the most commonly prescribed anti-HIV drug. Glaxo-Wellcome has described the Concorde study as flawed and said that its findings would not affect medical practice.

However, there are some eminent professionals ringing alarm bells. Dr Donald Abrams, professor of medicine and director of the AIDS program at San Francisco General Hospital has observed, "I have a large population of people who have chosen not to take any anti-retrovirals ... I’ve been following them since the very beginning... They’ve watched all of their friends go on the antiviral bandwagon and die." What united long-term survivors of AIDS was their resolve not to take AZT and other anti-retrovirals.

An article in last year’s June New Scientist reported that French doctors had linked a rare but fatal childhood neurodegenerative illness to exposure to AZT while still in the womb and during or shortly after birth. Dutch AIDS specialist Kees Brinkman, of Amsterdam’s Onze Lieve Vrouwe hospital, claims that several other side-effects may be explained by the drug’s ability to block the production of mitochondria, the energy-producing, semiautonomous organelles that are found in every living cell in the human body. "When continually assaulted, only weakness and eventual death can follow," he said. In a paper in Lancet last year, he and his colleagues added that there were other common side-effects, such as nerve and muscle damage, pancreatitis and decreased production of blood cells. Brinkman concluded, "I strongly believe that [these anti-viral drugs] are much more toxic than we considered previously."

An Italian study published last May in the journal AIDS claimed that HIV-positive mothers who took AZT had children with "a higher probability of developing severe disease or severe immune suppression and a lower survival [rate]" than those whose mothers had refused this treatment. A September Lancet article reported the cases of eight children with the obscure-sounding condition of "mitochondria dysfunction", two of whom died.

Building on this evidence, AZT critics say that the very symptoms of AIDS we have become familiar with, particularly severe wasting, may not be caused by the AIDS virus attacking the immune system but by the very drug claimed to cure it. If it is true that the treatment remains better than the disease, it is reasonable that doctors and researchers continue to recommend AZT. But could they be wrong? AZT was originally designed to kill cells indiscriminately. And to make matters worse, most people who go onto anti-retrovirals, including AZT, are completely symptom-free at the start. In fact, the main targets for the makers of these drugs are those without symptoms.

Dr Stephen Kent, senior research fellow at the AIDS pathogenesis research unit of the Macfarlane Burnet Centre for Medical Research in Melbourne, argued recently in The Australian (February 4) that the effectiveness of these drugs in reducing morbidity and mortality had been shown in countless studies since 1996. Dr Kent described the belief that HIV was not the cause of AIDS as a conspiracy with the potential to ‘mislead vulnerable people who are struggling with life-saving but difficult-to-manage HIV treatments".

Sceptical scientists claim the contrary — that there is still no study proving that any of these cocktails, separately or together, can extend life. In South Africa, material critical of AZT has become central to the debate, with claims that senior members of the AIDS medical establishment are unaware of the latest scientific literature. In a pointed rebuke of Dr William Makgoba, head of the Medical Research Council and a personal friend of Mbeki’s, the President said, "What do you do if professors won’t read articles about subjects they write about?"

Dr Kent has described the debate questioning existing treatments and research as "irrelevant" and "a disgraceful waste of time and resources". In a South African TV debate, a Glaxo-Wellcome representative said, "We find it unusual that these allegations of safety aspects on AZT have suddenly arisen in South Africa. They have not surfaced in any other country around the world, in over 100 countries where the drug is registered." To which the South Africa’s health minister replied "If it is the first time, then somebody has to start"

With billions of dollars in drug-company profits and research grants at stake, not to mention reputations, Mbeki is under enormous domestic and international pressure. Just two weeks ago his office bitterly accused Western drug companies of enriching themselves from the AIDS epidemic and compared them to warmongers "who propagate fear to increase their profits". In the face of nearly 20 years of research and the largest amount of money ever spent on a single virus (with precious little to show for it), it is surprising that the Western media is not taking more of an interest in these difficult questions.

Andrew McIntyre is a Melbourne writer who has written on HIV and AIDS for several years.