AIDS, AZT AND MBEKI PRICE,
NOT EFFICACY, IS THE ISSUE
By Claire Bisseker
Financial Mail (SA) 19 November 1999
The AZT scare triggered by government is a red herring - and a setback in the fight against AIDS, say the experts
AIDS does not exist. HIV does not cause AIDS. The traditional AIDS hypothesis is a wholesale fraud. In fact, the world's most commonly administered AIDS drug, AZT, causes AIDS.
Who would have thought that at the epicentre of the HIV/AIDS epidemic, where 1 600 people contract the HIV virus each day and the numbers of AIDS orphans and AIDS fatalities are mounting, these fallacies would be taken seriously?
But the aspersions President Thabo Mbeki has cast on the safety of AZT have opened Pandora's Box, and out have popped discredited Californian molecular biologist Prof Peter Duesberg and a dissident faction arguing - despite overwhelming scientific evidence to the contrary - that AIDS is a hoax. And they argue well, selectively quoting Nobel laureates and professors of medicine in support of their position. Constructing a conspiracy theory from half-truths must be a fascinating exercise - if you're not infected with the virus.
Mbeki told the National Council of Provinces in late October that he had asked the Health Minister to look into the claim in certain scientific literature that AZT is dangerous.
As a result of Mbeki's comments, his instruction that the Medicines Control Council (MCC) review AZT, and Duesberg's resultant appearance on prime-time television, HIV-positive patients have been thrown into confusion.
Medscheme's AIDS benefit management programme, Aid for AIDS, supports 3 000 HIV-positive members, of whom just over half are taking AZT. The programme's clinical co-ordinator, Dr Leon Regensberg, is being inundated with calls from fearful patients who think new evidence must have emerged about the drug's toxicity. One Cape Town patient has stopped taking AZT and his viral load has shot up dramatically, but he is convinced that he no longer has the disease.
Even Medical Research Council (MRC) president Dr Malegapuru Makgoba assumes there is new evidence on AZT. He says the MRC will, on its own initiative, review all information on the drug.
"Public concerns about AZT are said to be coming from scientific studies. We want to trace those studies and dig out the evidence, rather than dismiss it off-hand," he says, before asking whether the FM knows the source of the controversy. When we say it all comes down to Duesberg, he responds: "If it all comes from Duesberg, then I think it will amount to nothing. Duesberg can't even convince his peers in his own country. The problem is South Africans are so gullible. This takes away from all the good things we are doing in this country (to fight AIDS)."
Ten years ago Duesberg was a challenge, but his outdated theories have been buried under masses of incontrovertible scientific evidence. At the 1992 International AIDS Conference in Amsterdam, delegates sported badges stating, "It's the virus, you idiot!" in reference to Duesberg's theory that HIV doesn't cause AIDS. Then he was the butt of international jokes; now SA is, with the story making headlines in the US.
"We're making a laughing stock of ourselves," warns HIVCare International head Dr Ruben Sher. "Government is discrediting the drug because it doesn't want to pay for it. But it's backfiring, because there is no evidence... they will find nothing."
Many others in the medical profession, including ANC members and officials, regard Mbeki's statements as a setback in the fight against the disease, which infects 3,5m-4m South Africans.
"I've had a patient coming off AZT in trials because of all the publicity. It's irresponsible, the statements being made. We are losing a lot of the ground we've gained. It means government still doesn't want to take responsibility for the epidemic," says National AIDS Convention of SA (Nacosa) chairman and Cape Town's principal medical officer Dr Ashraf Grimwood.
"AZT is being singled out because government is trying to defend its decision not to provide it for mother-to-child transmission," says the head of Groote Schuur Hospital's HIV/AIDS Unit, Prof Gary Maartens. "It's pathetic; the MCC is toadying to the President. There's no medical or scientific reason whatsoever for the MCC to review the material. I'm sure the MCC will come out with a balanced report, but it's nauseating that they're even looking at it."
Dr Peter Moore, medical director of Glaxo Wellcome, the drug's manufacturer, says that as the Health Department is unable to put any new evidence on the table, Glaxo regards the MCC's review as "unnecessary and unjustified".
"On the contrary," says MCC chairman Dr Helen Rees, "we were in the process anyway, starting a few months ago, of looking at all the AIDS drugs. They have been introduced at huge speeds and for good reasons and when you do that, you have to look at safety. AZT is being used for things like needle-stick injuries and mother-to-child transmission, which is not what it was originally intended for."
She says the MCC will take an in-depth look at all data on AZT's safety and efficacy and will review the drug's registration status. The council will either tighten up on certain conditions or confirm the status quo. It should take at least a month. In the interim, Health Minister Manto Tshabalala-Msimang has recommended that people continue using the drug.
The World Health Organisation recently added AZT to its Essential Drugs List. The British government last month approved its use to reduce mother-to-child transmission of the virus.
Many people aren't aware of the background to Mbeki's statements on AZT - not that he found his speech material on the Internet, but government's long-standing row with Glaxo.
About three years ago, Glaxo met government in an attempt to dissuade it from parallel-importing AZT (getting it from a country where it is sold cheaper than in SA). Glaxo offered government a 75% discount, but government wanted the drug at cost. Glaxo's response was that this was not feasible. It expressed fears that AZT would be stolen from the State's porous warehouses and find its way on to the open market - a legitimate concern, but government was not amused. Relations deteriorated further when the pharmaceutical industry took government to court to halt subsequent legislation providing for the parallel importation of drugs.
"It was always about price, never efficacy," says an ANC source close to the talks. "The debate about the merits of AZT is a red herring. The real issue is how to get Glaxo and government to work together to get AZT to the people."
Providing HIV-positive people with AZT (at R600/month) in accordance with European monotherapy guidelines would cost about R5,6bn/year - a quarter of the entire health budget. No-one was suggesting government do this, but the clamour from pregnant HIV-positive women and rape victims for free AZT was becoming deafening and government's refusal difficult to defend.
Rees concedes that the MCC's investigation into AIDS drugs did not start with AZT, but with a newer class of anti-HIV (antiretroviral) drugs called protease inhibitors. This approach makes sense because AZT is the oldest, most tested, studied and commonly used antiretroviral in the world. More than 30 000 people have received AZT in clinical trials and about 300 000 are now taking it worldwide.
It is one in a class of five antiretrovirals licensed in SA called reverse transcriptase inhibitors. They prevent the virus from replicating in the same way. Therefore, dissidents who decry AZT because of its action (they claim it destroys the immune system and its effects are indistinguishable from AIDS) should be denouncing all the drugs in its class.
Their argument also ignores the fact that the epidemic is worst in sub-Saharan Africa, where few people have had access to AZT or other antiretrovirals.
AIDS-related deaths halved in the US from 1996 to 1997 because of highly active antiretroviral therapy, also known as triple therapy, where three antiretrovirals are administered simultaneously. AZT is commonly one of the three. Other Western nations experienced similar results, to the extent that they now regard AIDS as a chronic manageable disease, not a death sentence.
"More importantly," says Southern African HIV Clinicians' Society president Dr Des Martins, "published studies have shown that patients on combination therapy with AZT and 3TC have been able to maintain or improve their quality of life."
There are 12 antiretrovirals licensed in SA. All have side effects, except for Lamivudine, and some have as many side effects as AZT, if not more. If AZT was not beneficial and well tolerated, or was under genuine suspicion, doctors would switch to alternatives, and their peers in the litigious US would be too scared to prescribe it.
AZT was first licensed in 1987 in the UK, France and US, followed by SA in 1989. It is now licensed in more than 100 countries and the Centers for Disease Control in Atlanta (the world authority on communicable disease control) recommends its use by HIV-infected pregnant women. Glaxo Wellcome is unaware of any medicine regulatory authority, other than the MCC, that is reviewing AZT on safety grounds and says there are no legal challenges under way or pending against it.
The Southern African HIV Clinicians' Society has come out in support of the drug. "AZT is a valuable drug," says Martins. "We recognise that there are serious toxicities involved with AZT and all other antiretroviral drugs, as is the case with certain cancer drugs, and that patients on AZT therefore need to be monitored carefully."
Somerset Hospital HIV/AIDS Clinic head Dr Rob Wood has 200 patients on AZT. "It's not a toxic drug I avoid," he says. "Its side-effect profile is reasonable. I have many patients whose lives have been greatly helped from using it."
Aid for AIDS has 1 500 patients on AZT. "Over the past 18 months, fewer than 5% have reported significant side-effects or had to be taken off the drug for toxicity," says Regensberg. "There's ample evidence of AZT's efficacy and we don't believe its toxicity is a major problem, if monitored. Some of our patients have been on low doses of AZT for more than 10 years and are still doing well."
Though doctors are comfortable using AZT, all have high hopes for Nevirapine, which costs about R25/month and was found in a Ugandan study to be more effective than AZT in preventing mother-to-child transmission. Large clinical trials using Nevirapine are under way in SA. The results should be presented at the International AIDS Conference next July. If they are positive and the drug is licensed in SA, the medical profession will swing away from AZT for the treatment of mother-to-child transmission, says Dr Mark Cotton, a specialist in paediatric infectious diseases at Stellenbosch University.
Antiretroviral therapy does have severe limitations, however. It cannot cure HIV and patients are required to take multiple drugs for prolonged periods. There are also well-publicised concerns about long-term toxicity involving fat and glucose metabolism in some patients.
Press photographer Tyrone Arthur (34) is not alone in rejecting antiretrovirals. He was infected with HIV about six years ago. His last CD4 count was 135, compared to over 800 in a healthy adult. This means he qualifies for triple therapy under the rules of his medical scheme, which will cover the cost. But Arthur refused after learning about the side-effects of AZT, Heprivan and Crixivan, which could include diabetes and damage to the bone marrow. His homeopathic pills and oxygen therapy cost more than he would have paid for triple therapy but have no nasty side-effects and, besides, he feels well. Arthur should be sick in bed by now with AIDS, but he's productively employed.
"I am here to love life, not just to be alive. I still have fun and party hard, and I'm effective in the workplace," he says.
Those who argue that HIV doesn't cause AIDS, or that AZT makes you more sick, often use the example of long-term survivors. But studies show that less than 5% of those who test positive do not show evidence of declining immune function for about eight years and may survive 20 years without treatment.
All the medical experts interviewed by the FM say there is no credible scientific evidence to disprove the theory that HIV is the cause of the AIDS pandemic sweeping the world.
It is an exceptional case, they say, for someone to have a rare, AIDS-defining illness but not the HIV virus. Before the appearance of HIV, AIDS-like syndromes were rare; today they are common and epidemiological evidence shows a staggering rise in immunosuppression among individuals who share one characteristic - HIV infection.
Some dissidents argue that AIDS is a behavioural disease, hence its explosion in Africa. They like to quote Dr Gordon Stewart, professor of epidemiology at Glasgow University, as saying: "AIDS is a behavioural disease. It is multifactoral, brought on by several simultaneous strains on the immune system - drugs (including recreational), sexually transmitted diseases, multiple viral infections."
But Stewart was merely a professor of public health at the university between 1972 and 1984 and has no published work on AIDS in any reputable medical journal. His theory fails to explain why babies infected with the HIV virus develop AIDS and uninfected babies do not, or why these age-old patterns of behaviour have caused the emergence of AIDS only in the past 20 years. Another fallacy is the contention that the HIV virus has never been properly isolated. The entire genome of the virus has been isolated and analysed for many different HIV types. This has enabled scientists to begin to create AIDS vaccines using pieces of the virus' genetic material.
Some also question the accuracy of the HIV test, claiming it cross-reacts with pregnancy, thus explaining the high HIV rates in SA antenatal clinics. Others say the test is flawed because a co-founder of HIV, Dr Robert Gallo, wrongly identified HIV's markers (proteins) in 1984. The truth, says Clark, is that the initial tests were not based on the wrong markers, but were too narrow to detect the broad range of HIV types known to exist. "The current HIV Elisa tests are among the most reliable in modern diagnostic medicine."
The internationally standardised Elisa test used in SA has a sensitivity of 100%. This means it will not fail to detect a single HIV-positive result. It is followed by a second, confirmatory test to weed out any false positives that is 99,9% accurate.
The dissident faction's allegations go on. Refuting them is like convincing remaining members of the Flat Earth Society that the earth is round.
"SA's history of addressing AIDS is the most appalling debacle," says Grimwood. "We have shot our allies, knifed our neighbours and instead of attacking the enemy, attacked each other."
Maartens agrees: "In Uganda, they're winning the war against the epidemic because they had the political will to do so, not by believing in conspiracy theories."
What Mbeki has done is to politicise a stale scientific debate. The medicines regulatory authority in any country should be fiercely independent. Mbeki has crossed that line, again. He did it by supporting Virodene and accusing former MCC chairman Prof Peter Folb, who refused to bow to political pressure to license the industrial solvent, of professional dishonesty. Former Health Minister Nkosazana Zuma forever blurred the line when she pioneered legislation restructuring the MCC and replacing certain members with her own officials. Now Mbeki is casting aspersions on AZT.
It's like Virodene and Sarafina 2 again. This time fewer people will confuse political manoeuvring with hard facts.
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