September 18, 1997

U.S. AIDS Research in Poor Nations Raises an Outcry

By SHERYL GAY STOLBERG

WASHINGTON -- For the past two years, the United

States has been conducting experiments on pregnant

women infected with HIV in Africa, Thailand and the

Dominican Republic, in which some women are given drugs

that can prevent transmission of the deadly AIDS virus

to their babies and some receive only dummy pills.

The studies are so controversial that even some of the

government's own scientists have questioned whether

they are ethical. Now, one of the nation's most

prestigious medical journals has thrown a harsh

spotlight on the research, with an editorial that

likens it to the notorious Tuskegee experiment, in

which poor black men suffering from syphilis were left

untreated.

The AIDS studies, which involve 12,211 women in seven

countries and are paid for by the National Institutes

of Health and the Centers for Disease Control and

Prevention, aim to help the developing world find a

cheap, effective method of preventing transmission of

HIV to babies. The research is based on one of the most

dramatic discoveries of the AIDS epidemic: that women

who take the drug AZT during pregnancy can cut the risk

of transmission by two-thirds.

But the drug regimen, as used in the United States,

costs about $1,000 per mother, so public health

officials want to know if there are less expensive ways

to use AZT to achieve the same benefit. Half the

foreign women in the experiments receive AZT, at

varying levels that differ from the amounts used in the

United States. The other half get the dummy, or

placebo, pills.

As a result, critics say, more than 1,000 infants will

contract the AIDS virus, infections that the studies'

detractors say could be prevented.

"We have turned our backs on these mothers and their

babies," complained Dr. Peter Lurie of Public Citizen,

an advocacy group that has condemned the research.

Federal officials counter that the use of dummy pills

is the only way to get a quick, reliable result, and

that it is not depriving women of therapy they would

have otherwise received, since AZT is not affordable in

the Third World. But some critics suggest that this

argument is reminiscent of defenses offered for the

Tuskegee experiment, in which researchers watched the

ravages of syphilis while saying that the subjects of

their study, poor black men from rural Alabama, would

not have been treated in any case.

"Some of the same arguments that were made in favor of

the Tuskegee study many years ago are emerging in a new

form in the AZT studies in the third world," Dr. Marcia

Angell, the executive editor of The New England Journal

of Medicine, said in an interview this week. In

Thursday's issue of the journal, Dr. Angell writes that

the current AIDS research represents a "retreat from

ethical principles."

The use of dummy medication has always been

controversial in medical research, but never more so

than with studies involving AIDS. In the United States,

advocates for AIDS patients have all but eliminated

placebo-controlled clinical trials by demanding that

every patient have access to some kind of drug therapy.

But the same is not true in the developing world, where

many can barely afford aspirin, let alone expensive

medicines like AZT.

Nonetheless, the journal editorial has touched off an

intense debate about whether the mother-to-infant

transmission studies should continue. Several experts

in medical ethics said they had urged officials at the

health institutes and the disease-control centers to

abandon the studies, or at least reconsider. The

National Bioethics Advisory Commission may address the

matter when it meets in Washington this week.

"If you tried to do this study in the U.S., you would

have to do it through a throng of demonstrators and a

sea of reporters," said Dr. Arthur Caplan, director of

the Center for Bioethics at the University of

Pennsylvania. "I wouldn't do this study without a

design that would let me run it without a placebo. I

think you owe that to your subjects, even if they are

not educated enough, savvy enough to demand it from

you."

Still, Caplan says, the Tuskegee analogy is

inappropriate because the Alabama men were falsely told

that they were getting treatment. Others agree, and say

that that there is nothing wrong with U.S. researchers'

tailoring their studies to the health care systems of

other nations, without regard to standards here.

"The facts are different in different places," said Dr.

Norman Fost, director of the medical ethics program at

the University of Wisconsin.

At the health institutes in Bethesda, Md., and the

disease-control centers in Atlanta, officials scrambled

Wednesday to defend the experiments, saying that

officials in the foreign countries chose to use dummy

medication in the studies, and that U.S. standards

simply could not be translated overseas.

Privately, they worried that the outcry would force

them to cancel the research, a move that they said

would cripple their efforts to control AIDS in

countries where it takes its most devastating toll.

"This wasn't something that we did behind closed

doors," said Dr. Helene Gayle, who directs the AIDS

program at the disease-control centers. "This was done

with a lot of discussion from the international

community, following international codes of ethics.

Part of doing ethical trials is that you are answering

questions that are relevant for those countries."

If HIV-infected women are not treated with AZT in

pregnancy, roughly 25 percent of their babies will be

born infected with the virus. If they are treated with

the drug, the figure falls to 8 percent or lower. In

the United States, roughly 8 percent of all babies born

to HIV-infected women -- fewer than 500 a year -- are

born infected. But the disease-control agency estimates

that around the globe, more than 1,000 infants are born

infected every day.

"In our wards, 30 percent of children admitted each day

are HIV-positive," said Dr. Glenda Gray, a pediatrician

in South Africa who is taking part in similar studies

paid for by the United Nations. "I've buried hundreds

of children. I'm seeing their mothers die. We need to

find a magic bullet for every woman in the world."

Finding that magic bullet will not be simple, Dr. Gray

and others say. In the United States, AZT is given

during the final 12 weeks of pregnancy. Women also

receive an intravenous infusion of the drug during

delivery, and their babies take the medicine for six

weeks after birth. This is commonly called the 076

regimen, which gets its name from the number assigned

to the federal study that proved it effective.

But the regimen has problems in developing countries.

Aside from the cost, many nations do not have the

equipment to administer AZT intravenously. And most

mothers in the Third World breast-feed, a practice that

can spread the virus to infants and that can counteract

the benefits of taking the drug during pregnancy.

Thus in 1994, after the results of the 076 study were

published, officials at the World Health Organization,

the United Nations, the National Institutes of Health

and the disease-control centers gathered in Geneva to

design clinical trials suitable for overseas. In the

absence of any standard of care, said Dr. Joseph Saba,

a U.N. AIDS official, they settled on comparing

different courses of AZT to dummy medications.

Almost from the outset, there was controversy. In

January 1995, government records show, CDC

investigators in the Ivory Coast wrote to the agency's

headquarters in Atlanta to say that several of their

African collaborators "do not feel comfortable with the

use of placebo."

At the same time, Marc Lallemant, a Harvard University

investigator working in Thailand on behalf of the

health institutes, insisted he would not use dummy

medication. Dr. Troyan Brennan, head of the Harvard

University ethics panel that reviewed the study, said

in an interview that because the Thai government had

indicated that it could offer AZT to pregnant women,

his committee did not consider dummy medications

"ethically appropriate." None of the Thai women in the

institutes' study receive placebo. But some Thai women

in a disease-control agency's study get the dummy

pills.

Then, in April, Public Citizen wrote to the secretary

of health and human services, Donna Shalala, to argue

that it would be just as scientifically valid, albeit

more expensive, to compare a short course of AZT to the

longer 076 regimen. Lurie argues that when scientists

work in another country, they have an obligation to

give their patients the best care possible, regardless

of what the local standards of care are. In an

interview, Dr. Angell supported that view.

"If you say it's all right to have a different standard

in the Third World," she warned, "that is opening the

door to a real slippery slope."

Yet Dr. Gray, the South Africa pediatrician, said there

was a far more pressing concern. If the current

studies, which are to be completed in six months to a

year, find that a short course of AZT is effective, she

asked, will the authorities who financed them pay for

women in her country to get the drug? "If they're

really concerned about the ethics of placebo," she

said, "they should put their money where their mouth

is."