Newsday - October 17, 1989
Laurie Garrett

Specialists in treating AIDS said the possible risks of AZT toxicity are more than offset by the dire likelihood that children born infected with HIV, the AIDS virus, will die.

Currently, there is no way to tell whether a fetus or newborn is infected with HIV. At least half the offspring of infected mothers are born virus-free.

But those who are infected "usually develop disease more quickly than adults do," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "Of those diagnosed before their first birthday, half die within six months of diagnosis."

The intent of the program is to see if AZT will keep the AIDS virus from passing from the infected blood or milk of the mother to the baby; barring that, doctors hope to block permanent infection in exposed newborns.

"It is impossible to count the costs in pain and heartbreak, and the social and economic burden of caring for these children is staggering," Fauci said. "This study is vitally important in our effort to find ways to reduce the chances of transmission from mother to baby."

In adults, however, AZT can rarely be tolerated for more than 18 months, because the drug destroys bone marrow cells and causes life-threatening anemia. Recently a French research team discovered AZT causes severe birth defects in rats when given during all stages of pregnancy in doses roughly comparable to those researchers are using on pregnant women.

"People ought to be very clear about what they are doing here," Dr. Carol Levine, executive director of the New York City Commission on AIDS, said in an interview. "I think it's very troubling, particularly since the majority of these women and children are [members of] poor minorities."

Levine noted that the experimental administration of a toxic drug to possibly healthy fetuses and newborns "is unprecedented" in American medicine. "There ought to be considerable concern about the consent" of the mothers involved, Levine said. Federal officials said they will carefully monitor the ethical guidelines of the studies, which will be administered by hospital research boards across the country.

A handful of women have taken AZT without knowing they were pregnant; the drug did cross their placentas without damaging the fetuses, according to Dr. Ed Connor of Children's Hospital in Newark. Studies of AZT use in rabbits and mice indicate viral infection can be blocked if the drug is taken immediately after exposure to HIV, he said. "We're looking at the idea of using AZT for just six weeks," said Connor, "during the third trimester of pregnancy or shortly after birth. Toxicity usually occurs after six weeks," so the risks of AZT should be relatively low.

Other institutions have already been looking at the safety issue. With neonatal AZT tests "80 percent done," Dr. John Modlin of Johns Hopkins University said he finds the drug safe for babies. It's too soon, he said, to draw conclusions about the utility of AZT in babies, but "you need to remember that if this drug is going to be used effectively, it will be in this age group." Studies show that once HIV has taken hold in children, no drug - including AZT - can reverse the course towards AIDS and death. That means, Modlin said, that doctors have no choice but to treat fetuses and babies before they have reached the age at which it is possible to tell whether or not they are infected.

"The only ethical problem I would see with this would be if AZT caused harm to either the mother or fetus," said Modlin. "Other than that, I don't see any ethical problems whatsoever. There is plenty of precedent - take syphilis. We give penicillin to pregnant women. I just don't see what the ethical hang-up would be."

Connor asserted, in an interview: "Women need reproductive options. I am not in that business, but I am in the business of making sure I provide optimal therapy. The only way we can do that is by diagnosing HIV infection in sexually active women as early as possible, so we can anticipate their needs."

Both Modlin and Connor say the majority of HIV-positive women are poor and have little, if any, prenatal care. As a result, they often have no knowledge of their HIV status until after they give birth to a sick baby. Among those who are aware of their infections during pregnacy, fewer than 10 percent opt to abort the possibly infected fetus.

"The point is," said Connor, "there is a mandate, medically, to come up with an alternative: to block infection [of the fetus or newborn]."

Bioethicist Dr. Ronald Bayer of Columbia University said in an interview, "No woman should be denied access [to AZT] because she is pregnant." He noted that medical ethics have traditionally viewed the pregnant woman and child as individuals in need of special protection in research, with the result that considerably fewer experiments are performed in obstetric and pediatric medicine. "The level of risk tolerated for research on children is incredibly low," said Bayer, "so people are beginning to talk about stretching those limits" for AIDS research.

Bayer said as far as he is concerned the fundamental ethical dilemma is not protection of the mother and child but drug access. To date, the Food and Drug Administration has refused to grant approval for the obstetric and pediatric use of any of the AIDS drugs now available to adult males.

Many pediatricians working in areas of high HIV prevalence are now telling the FDA and the National Institutes of Health that the time has come to dramatically expand experiments on fetuses and babies. Pediatrician Stanley Plotkin of the Wistar Institute in Philadelphia thinks babies may be the only clinical pool left for AIDS drug trials. At a recent meeting of the National Academy of Sciences in Washington, Plotkin noted that it is impossible to organize a well-controlled clinical trial of AIDS drugs in adults, because participants usually take other treatments simultaneously, with or without physician approval, and drop out of studies the moment they suspect the research drug is proving useless or harmful. Children, on the other hand, comply with doctors' orders.

"When one considers pediatric patients have a fifty percent mortality in two years," added Plotkin, "one can see it would be easy to include death in a drug test outcome." Adults infected with HIV are now living an average of 11 years from the time of diagnosis, meaning clinical trials that follow adults throughout the course of HIV infection would take more than a decade to complete.

Plotkin argued officials with the FDA and NIH should step up the pace of pediatric AIDS drug research: "It's becoming unethical to not use AZT. We need to do these studies rapidly in kids before the pressure comes to use those drugs we have already which may not be optimal."

"I find it a little peculiar to advocate trials on children just because they are unconsenting," countered Levine. "The point may be valid [that children are more likely to be compliant] but I don't think it's an argument to do more research on kids."

While debate continues over just how much scientists should relax special protections of pediatric research subjects, Levine warned that the rights of pregnant women have been seriously limited by recent court rulings. Judges in eight states have ordered addicted women to undergo drug rehabilitation to protect their fetuses from cocaine and heroin. In several states women have faced court orders to submit to medical procedures on behalf of the fetus.

"I really dislike this trend toward seeing the pregnant woman as the natural enemy of her fetus," said Levine. In such an atmosphere, she continued, there is the spectre of courts ordering HIV-positive pregnant women to take AZT or other AIDS drugs believed to be beneficial to the fetus. "That day may be coming," she said, "and I would like to postpone it as long as possible."

Bayer was adamant that such concern should not be allowed to hold up research on pediatric and obstetric AIDS treatments. "We have to be very careful," he said, "and say we're willing to go this far and no further. But to hold up the threat of the slippery slope is to stagnate. Not intervening medically because of such fears is, in itself, a form of intervention."

Pediatric and obstetric AZT trials are, or soon will be, under way in Newark, Baltimore, San Francisco, Los Angeles and Miami.
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