TRUTH AND LIES ABOUT AZT

By Aaron Nicodemus

The Mail & Guardian (SA) 1 Dec. 1999

With the AIDS crisis at the forefront of health issues, Aaron Nicodemus examines Minister of Health Manto Tshabalala-Msimang's stand on AZT.

At an AIDS breakfast sponsored by the SABC last week, Minister of Health Manto Tshabalala-Msimang once again dismissed the anti-retroviral drug AZT. She said it is too expensive, and that even with a significant discount provided by manufacturer Glaxo-Wellcome, providing the drug to the nearly four million HIV-positive South Africans would break the health budget. Based on all the evidence, that statement rings true.

However, hardly anyone is asking the government to do that. Slowing the disease's spread would be more realistic. What about providing anti-retroviral drugs to HIV-positive pregnant mothers, to cut down on the transmission of the disease to their children? Or to health workers infected by tainted needles? Or, perhaps most controversially, to victims of rape?

The minister said: "There is not substantial data that AZT stops the transmission of HIV from mother to child. There is too much conflicting data to make concrete policy."

South African government officials might deem the data on AZT too conflicting to make a judgment, but other governments have not. Based on a landmark 1994 AZT study in the United States and a US-sponsored study completed in Thailand in 1997, the US Center for Disease Control has a written policy of providing AZT to HIV-positive mothers. In the US, women receive four weeks' worth of anti-retroviral drugs to cut down the possibility that the child will become infected.

Providing anti-retroviral drugs to HIV-positive mothers has become standard treatment in Canada, Britain and most western European countries. For 10 years, AZT has been registered with the Medicines Control Council in South Africa for the purpose of cutting down HIV-transmission rates from mother to child.

Peter Cooper, head of paediatrics at Johannesburg hospital and the University of the Witwatersrand, said the minister's statement "is complete nonsense". He said that providing AZT to HIV-positive mothers could cut in half the estimated 60 000 children born with HIV in South Africa every year.

Cost and the logistics of distributing AZT are legitimate concerns, he said, but no one in international scientific communities is questioning the drug's effectiveness. "It's like believing the earth is flat," Cooper said.

The minister said: "South Africa is the only country in the world who gives AZT to health workers for needle-stick injuries. It's very doubtful that we're doing the right thing."

Not true. The US Center for Disease Control's standard policy on treating needle-stick injuries is a 28-day course of anti-retroviral drugs, of which AZT is currently the most prominent. Britain's National Health Service made a similar recommendation earlier this year.

The minister said: "As to rape victims, I have engaged in a dialogue with Glaxo-Wellcome, and checked all of their policy documents. Nowhere does Glaxo-Wellcome advocate using AZT to prevent the transmission of HIV to rape victims."

The company's medical director for sub-Saharan Africa, Dr Peter Moore, said the minister's statement is technically true. There are no studies on rape victims and AZT because it is nearly impossible to conduct conventional drug trials with rape victims. Despite that, the US Center for Disease Control recommends that patients and their doctors consider using AZT for rape victims after weighing the risks and benefits for the individual patient. The centre allows that there are legitimate arguments to be made on both sides. But without clinical trials, the agency cannot make a definitive policy statement in these circumstances.

The minister said: "The fact is that some of the mice [tested on with AZT] have contracted cancer. It attacks bone marrow. It is very toxic."

Moore said AZT's toxicity has been well-documented. In the 28-day treatment of pregnant mothers and for needle-stick injuries, Moore said several studies have found no evidence of permanent side effects. Long-term use of AZT does contain risks, including cancer, anaemia and a reduced white blood cell count. These side effects develop in about five percent of patients who use the drug for more than six months, Moore said. "One has to look very carefully at the possible effects and benefits of any drug," he said. "Why is AZT being singled out?"

Charlene Smith, a journalist who has been campaigning to have the government provide anti-retroviral drugs to rape victims, said the answer is simple: "Stop giving AZT to the damn mice and start giving it to people."

The minister said: "AZT was never meant to treat HIV. It was meant to treat cancer and, when it was discovered to be toxic, the drug companies stopped clinic trials of the drug because it was so toxic. Is this drug really one we want to use?"

The minister's version of events leading to the development is misleading, Moore said. AZT was developed as an anti-cancer agent in the 1960, but it was not found to be effective. It was shelved. When AIDS came on the scene decades later, the drug was screened against the virus and found to be effective, he said. "This is nothing new. If AZT is not safe, why has it been allowed on the market in South Africa for 10 years?"

The minister said that 75% of HIV-positive women do not transmit HIV to their children. Only 25% of those children contract HIV, she said. "Could you, with a clear conscience, introduce those toxic drugs to a woman and her child? I say no."

In other medical interventions, averting disease in 25% of patients is viewed as exceptionally good. South Africa provides vaccinations for measles, for example, when less than 10% of children would ever contract the disease. Less than 1% of children contract whooping cough, yet vaccinations are offered to all children in South Africa. With any vaccination there is a chance of side effects.

What doctors and patients should do is make a judgment call about whether the benefits of taking the drug outweigh the risks.

"On this score she is wrong," said Professor Salim Abdool Karim, head of AIDS research for the Medical Research Council. "Public health is based on the principle [of benefit versus risk]. If she doesn't agree with that principle, she might as well shut down the health department and go home."

Recent medical research contradicts the minister's statement.

Studies based in the US and France indicate that AZT can cut the transmission of HIV from mother to child by between 50% and 75%.

The long-term side effects in children have also been studied. A US study conducted by researcher Mary Smith for the Nucleoside Safety Review Working Group was presented to the Montreal Mother-to-Child HIV meeting in September of this year. The study tracked 15 500 HIV-negative children whose HIV-positive mothers were given a four-week treatment of AZT. Over the course of five years, the children were found to have contracted no adverse side effects, including cognitive function, hearing and overall health.

Another study, published in the Journal of the American Medical Association in January 1999, followed 332 infants for more than five years. The study also found no long-term side effects associated with children whose mothers took AZT during pregnancy.

The minister said: "Until we are convinced that the drug AZT is safe, as a responsible government we will not move in that direction."

Researchers, hospital administrators, NGO directors and AIDS counsellors are baffled at the government's outright refusal to consider any anti-retroviral therapies in the fight against AIDS. They can offer no explanation for the "missionary zeal" with which now two health ministers have condemned a therapy that is widely established internationally in the fight against AIDS.

But let's assume for a moment that Tshabalala-Msimang is right about AZT, that it is simply the worst and most dangerous possible drug for use in curbing the country's ballooning AIDS epidemic. AZT is merely one brand name in a field becoming populated by more choices. What about a generic equivalent? What about the German drug Nevirapine, which has been found to be just as effective as AZT, less toxic and less expensive?

But the government has already weighed in on the new drug, expressing concerns about "resistance". What exactly is the government waiting for?

In discussing AZT, Tshabalala-Msimang has mentioned that a vaccine for AIDS is being developed in South Africa. Karim, who is heading up that project, said the vaccine, if proven successful, is seven to 10 years away from being widely available. Should the government not consider some other medical intervention for HIV during that intervening decade?

Or should it only wear AIDS ribbons, provide condoms and stand aside as the world's fastest-growing AIDS epidemic continues to claim millions of victims?