The Associated Press; 50 Rockefeller Plaza, New York, NY 10020 - Wednesday, September 17, 1997; 5:57 p.m. EDT
Daniel Q. Haney, AP Medical Editor

An editorial in Thursday's issue of the influential journal compares the research efforts to the notorious Tuskegee study in which penicillin was denied to black men infected with syphilis.

It argues that withholding proven AZT treatment from pregnant women with AIDS, even in places where the drug will never be widely available, clearly violates World Health Organization guidelines intended to keep researchers from conducting unethical experiments.

Every day around the world, at least 1,000 babies catch HIV from their mothers. Sixteen research projects, mostly in Africa, are trying to find affordable alternatives to weeks of AZT treatment, now the standard approach in prosperous countries to prevent infected mothers from passing on the AIDS virus in childbirth.

The proven AZT regimen costs $1,000 per pregnant woman and is simply out of the question in countries where total per capita spending on health care is less than $10 a year. As a result, most of such AIDS-infected women get no preventive treatment at all. The goal is to find some level of treatment that will work with as little as two or three pills and cost a few dollars.

To prove that simple approaches work better than nothing, researchers have set up comparison studies in which some women get low doses of drugs and some get dummy pills.

The researchers contend this is the only practical way to quickly solve this health crisis, but their use of placebos raises one of the touchiest issues in international medical research -- whether experiments that would never be considered in the United States or Europe should be done on the poor abroad.

The landmark U.S. study proving AZT's power to reduce AIDS transmission gave placebos to a comparison group of HIV-infected women because the drug was then unproven. Now, AZT is given to all comparison groups in U.S. studies looking for even better treatments.

Dr. Jack Killen, head of the National Institutes of Health's Division of AIDS, acknowledges that ethical principles in research sometimes conflict. And in this case, he said, it is most important to find information that will eventually help the people being studied.

"What we need to know is whether a medical intervention is better than nothing," Killen said. "Any other experimental design would not answer that question and would be an even more unethical thing to do."

The editorial was written by Dr. Marcia Angell, the journal's executive editor. It accompanied a detailed critique of this kind of research written by two members of the Public Citizen Health Research Group, a Washington-based advocacy organization.

Angell notes that international rules require comparison groups to receive the best treatment available, not simply the standard in use where the study is being conducted.

In her view -- and those of Drs. Peter Lurie and Sidney M. Wolfe of the Health Research Group -- this means everyone treated in these studies should get AZT.

"The standard of care in the developing world is nothing, because these countries are poor and the drug is overpriced," Lurie said. "To use those social conditions to justify this research is exploitive and unethical."

Lurie first complained about the studies in a letter to Health and Human Services Secretary Donna Shalala in April. In his journal article, he contended that researchers can ethically compare shorter doses of AZT to the full treatment but should not withhold the drug entirely.

According to Lurie, 14,215 women are enrolled in ethically questionable studies in Burkino Faso, Ethiopia, Ivory Coast, Kenya, Malawi, South Africa, Tanzania, Uganda, Zimbabwe, the Dominican Republic and Thailand. Less than a third of the women are getting AZT.

Lurie targeted 15 of the 16 current studies for ethical breaches, nine of them funded by the U.S. National Institutes of Health or the U.S. Centers for Disease Control and Prevention. Five are financed by other national governments, and one is backed by the United Nations AIDS Program.

"The justifications are reminiscent of those for the Tuskegee study," Angell wrote.

That experiment, begun in 1932, studied the natural history of syphilis by following poor black men at a time when no good treatment was available. The study continued after the discovery of penicillin made syphilis curable, but the subjects weren't offered the antibiotic on grounds such patients wouldn't have been treated anyway.

Defenders of the AIDS studies dismiss the Tuskegee comparison.

Dr. Catherine Wilfert, medical director of the Pediatric AIDS Foundation, said the editorial was "calling on people's emotions rather than dealing with the facts in the case."

Cost is only one barrier to standard AZT therapy for pregnant women in much of the world, Wilfert said. Another is the almost complete absence of prenatal care, which means there is no way to administer the drug throughout pregnancy.

"The decision to go ahead with a placebo-controlled trial, although not an easy one, was a consensus among research institutions and people from developing countries," said Dr. Joseph Saba, who directs a U.N. AIDS study in Africa of the drugs AZT and 3TC.

Without an untreated comparison group, he said, it would be impossible to know whether low doses of a drug are truly better than nothing at all.

Saba and others also question whether the results of the original U.S. study on AZT even apply in Africa.

HIV spreads through breast milk. Infected U.S. women are routinely told not to breast feed, but this advice is not practical in poor countries, where women have no alternative. The researchers said any beneficial effects of AZT given during pregnancy could be wiped out by subsequent breast feeding.

Copyright 1997/The Associated Press. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, The Associated Press, 50 Rockefeller Plaza, New York, NY 10020.
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