Setting off an angry debate, a pre-eminent medical journal has charged that the Johns Hopkins University and other institutions planning AIDS prevention trials in Africa violate ethical standards by withholding proven treatments from participants.
In a strongly worded editorial, the New England Journal of Medicine said the trials show that U.S. researchers haven't learned much from the notorious Tuskegee experiment, when public health authorities in Alabama withheld treatment from black men who had syphilis.
Reviving criticism raised in the spring by a public interest group, the usually staid medical journal said that the experiments "signal a retreat from ethical principles."
The editorial's subject was 16 experiments, most in Africa, that are designed to find inexpensive, practical ways to prevent mother-to-baby transmission in nations where per-capital health expenditures amount to mere dollars each year. The proposed therapies include vitamin A and short courses of the drug AZT.
The experiments compare the techniques against placebos -- a tool that scientists say represents the absence of treatment prevalent in those countries.
But the journal contended that scientists should compare the low-tech methods to proven therapies, such as the $1,000 regimen of AZT that is now considered the standard of care in the United States. In the so-called "076 protocol," AZT is given orally to women late in pregnancy and intravenously during labor. Oral doses are also given to the babies in their first six weeks.
Three years ago, the protocol was shown to reduce transmission by two-thirds.
"Only when there is no known effective treatment is it ethical to compare a potential new treatment with a placebo," said the editorial, signed by Executive Editor Marcia Angell. "When effective treat- ment exists, a placebo may not be used. Instead, subjects in the control group of the study must receive the best known treatment."
The editorial struck a nerve among researchers, who contended that it would be unethical to introduce an expensive treatment that the countries cannot afford -- and then withdraw it when the experiment is over.
"You don't want to deny treatment to anyone who would otherwise get the treatment," said Dr. Alfred Sommer, dean of the Johns Hopkins School of Hygiene and Public Health, which has roles in five of the trials in question. "You're going into Africa where nobody gets anything because the drug is too expensive.
"Even if you gave the drug, they don't have the infrastructure. They don't have the IVs. They don't have the laboratories. Most ** deliveries are not even attended."
Sommer said placebos also allow researchers to determine the rate of mother-to-baby transmission in countries where women get little or no care. He said the rates can vary from country to country, where nutritional status and overall health differ, and they permit scientists to see whether a proposed treatment really makes a difference over what normally exists.
Dr. Jack Killen, director of the AIDS division at the National Institute of Allergy and Infectious Diseases, said critics don't understand the realities of public health in the Third World.
"In a country where the annual health expenditure is $25, the 076 regimen is a total nonstarter. It's just not even relevant. It has profound ethical considerations," he said.
More than 1 million children worldwide have been infected with the human immunodeficiency virus through mother-to-infant transmission, according to government estimates. Most infections occur in developing nations, where an estimated 300,000 infections are now occurring each year.
The studies in question are scheduled for Africa, Asia and the Caribbean. Hopkins is planning studies in Ethiopia, Uganda and Malawi. Another trial once slated for the Dominican Republic has been canceled for reasons unrelated to the controversy, according to its principle investigator.
The Hopkins studies are being funded by the National Institutes of Health; other experiments are being sponsored by the United Nations and the U.S. Centers for Disease Control and Prevention.
The editorial amounts to an endorsement of a position taken in April by the Public Citizen Health Research Group, which compared the studies to the government's Tuskegee experiment, a four-decade study on untreated syphilis.
Researchers, Angell said, are violating ethical codes requiring that human subjects receive "protection at least equivalent to that in the sponsoring country."
This week, the journal also carried a position paper by Dr. Sidney Wolfe, Public Citizen's director, and Dr. Peter Lurie, a researcher with the group, in its "Sounding Board" section.
In an interview, Lurie said defenders of the studies raise a "red herring" by arguing that the countries lack the means to offer effective AZT treatments to their people. The question of what countries can afford is one for the local authorities to decide, he said, not U.S. researchers.
Lurie called for an "equivalency" study -- one that seeks to see if alternative treatments are nearly as good as the most effective ,, known therapy.
"The infrastructure thing has been overrated," Lurie said. "No one has really made a systematic attempt to understand what it is that these people can afford. To look half the women in the eye and deny them the intervention that stands a one-in-seven chance of saving their babies' lives is inconsistent with every standard of medical ethics."
The controversy sparked a Senate hearing and led Health and Human Services Secretary Donna E. Shalala to order a review. The review was conducted by NIH director Harold Varumus and CDC director David Satchert, who concluded that the experiments were proper and had been approved by officials in the host countries.
Dr. Neal A. Halsy, a Hopkins professor of international health, said the New England Journal was wrong not to allow comparable space to researchers involved in the studies.
"The New England Journal has violated an important principle of reporting," he said. "They are reporting a tiny minority perception -- and it's a misperception -- without reflecting the detailed review done by the CDC, NIH and HHS."
Pub Date: 9/18/97