Map of life expectancy at birth from Global Education Project.

Monday, December 15, 2008

Bloodletting

In 1987, the FDA approved the first drug to combat HIV, most commonly called AZT, generic name zidovudine, also called Retrovir. Doctors began to prescribe it in high doses to control replication of HIV and, presumably, the progression of HIV disease. Technically, AZT is what is called a nucleoside analog reverse transcriptase inhibitor, a class of drugs which people with HIV know by the slang term "nukes." Reverse transcriptase is the enzyme which causes the HIV genome to be incorporated into the DNA of the host cell, the signature process of a retrovirus. NRTIs like AZT work by mimicking one of the chemicals that constitutes a "letter" in the genetic code. They get picked up by reverse transcriptase which attempts (pardon the attribution of intention, it's a convenient figure of speech) to incorporate them into the growing DNA chain, but they don't work properly, and the transcription process terminates.

In the early 1990s, I had occasion to talk with many people living with HIV, in focus groups, formal research interviews, and informally. Some people were taking AZT, but at least as many told me that as far as they were concerned, it was worse than useless. Some of them had tried it and had suffered intolerable side effects. All of them had watched friends take it and seen them suffer side effects, and nevertheless sicken and die from AIDS.

During this era, many people came to the conclusion that the story scientists were telling about HIV was erroneous, that HIV was not the cause of AIDS. Some even described it as a fraud. Among these were some prominent virologists, who eventually convinced among others Thabo Mbeki, who became president of South Africa in 1999. The story of so-called AIDS Denialism is complicated, but the evident ineffectiveness of AZT, even as scientists and doctors continued to push it aggressively as the treatment for HIV disease, was a main fuel of the movement. You can sample their arguments here. This is a link page which I utterly abjure, repudiate, reject and denounce. I offer it as a social artifact of considerable importance. Click on the home page link, and you will get an overview of the movement and, in particular, its association with now former president Mbeki.

Well guess what? In 1993, a British study called the Concorde trial proved definitively that AZT, by itself, did nothing to delay progression to AIDS or to increase life expectancy. All those regular folks were right, and the doctors were wrong. We have visited this issue here many times -- approval of drugs because of what are called "surrogate" endpoints. AZT was approved because it inhibits viral replication and reduces viral load, not because it had been shown to have any clinical benefits.

It turns out that AZT is useful after all, but only in combination with other drugs. A so-called "cocktail" of antiretroviral drugs can suppress viral replication sufficiently to delay progression of HIV disease, even to bring back people who are near death to a state of reasonably good health. (AZT, by itself, is also useful for preventing transmission of HIV from mother to baby, although it is no longer the drug of choice for this purpose.) But by the time this was understood, it was too late to stop the denialism movement from doing grave harm, particularly in South Africa.

Next: Stigma, prejudice, and HIV as an instrument of oppression

3 comments:

kathy a. said...

i've had a lot of trouble understanding where AIDS denialism came from. my reaction to mbeki's rejection of HIV as the cause of AIDS was that the man was simply delusional.

since i live in the S.F. area, the news that has caught my eye has been along more postive lines -- and drug cocktails have produced such amazing results over an extended period of time that it is hard for a lay person like me to remember how bad things were before that.

Cervantes said...

that's correct -- it's undeniable that the so called HAART (Highly Active Anti-Retroviral Therapy) combinations work, and that convinced most people. But we need to remember the period of several years in which doctors were in fact poisoning people for no actual benefit. That's largely where it comes from.

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AZT was approved because it inhibits viral replication and reduces viral load, not because it had been shown to have any clinical benefits.