Fateful Decisions on Treating AIDS

By Ezra Bowen

You're the doctor, and the patient is dying from AIDS. A new drug called azidothymidine (AZT) might temporarily suppress the virus and prolong his life. But you hesitate: AZT may do nothing for his manifestation of the disease. It could even hasten death. And prescribing the drug could bring malpractice suits, since AZT has so far worked only on AIDS sufferers with symptoms different from this patient's.

Do you let him go? Or do you risk everything on the chance of helping him?

These questions took on new urgency last week when the Anti-Infective Drugs Advisory Committee of the Food and Drug Administration recommended by a 10-1 vote that the FDA approve AZT as the first commercially available treatment for AIDS. The news generated heavy demand from America's 13,000 AIDS victims. For among potential AIDS drugs being tested, only AZT seems to prolong life, specifically for people with Pneumocystis carinii pneumonia (PCP). The prospect of public release intensified ethical concerns surrounding not only drugs for AIDS treatment but also vaccines to prevent it.

Indeed, an ethical concern prompted researchers last year to cut short clinical experiments on PCP patients. In six months only one of 145 AIDS patients given AZT died; many of the others grew stronger and regained some sense of well-being. (Since then, eight more have died.) In a like-size control group given only medically inactive substances, or placebos, 16 perished. These dramatic results prompted Burroughs Wellcome, the North Carolina firm that developed the drug, to call off the trial and immediately begin giving AZT to all the test patients. Many doctors hailed the decision, including Charles Schable, chief of the AIDS Diagnostic Laboratory at the Centers for Disease Control in Atlanta. "I don't see how you can have a placebo group," he said, "because if you're pretty sure it's going to work, why should you not give it to people?"

But halting the test robbed researchers of the chance to judge, under controlled conditions, any long-range effects of AZT, which might be as dangerous as the untreated disease. In fact, some people taking AZT have developed anemia and suffered bone-marrow degeneration. "AZT may be a genie that we are letting out of the bottle," says Dr. Itzhak Brook, chairman of the FDA advisory committee and the only dissenter in the vote. Dr. Maxime Seligmann, a French immunologist who has experimented with AZT at the Hopital St.-Louis in Paris, agrees: "There simply isn't enough knowledge about the benefits of the drug compared to the toxic effects and long-term risks."

Another troubling consequence of releasing the drug is its likely restriction to AIDS patients who have had PCP (about 60% of all victims). Without further tests, doctors cannot tell what the effects will be on those with other variations of the disease. Says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases: "There is an ethical dilemma of doctors using AZT beyond the categories where the drug has been proven safe and effective."

Even more distressing is the certainty that AZT will be in short supply, at least for a while. Arthur Caplan, a medical ethicist at the Hastings Center at Hastings-on-Hudson, N.Y., calls the shortage a "classic triage" situation. "Who do you give it to?" he says. "You're not going to throw the drug away on someone who is so desperately ill that he will die anyway." He is also inclined to withhold it from drug abusers, who, along with homosexuals, are the principal AIDS sufferers and might waste the treatment by reinfecting themselves. Nor does he feel anyone but medical professionals should decide. "Desperately ill patients are not in a position to make that choice," he says.

Richard Dunne, executive director of the Gay Men's Health Crisis in Manhattan, takes issue with Caplan. "I don't think researchers understand at a feeling level the predicament of a dying person who hears of something promising," he says. "Human beings have a right to make their own choices."

Doctors and researchers are also struggling with the ethics of testing potential AIDS vaccines now under development in the U.S. and France. The problem: vaccines for any disease must eventually be tested on healthy humans. What if volunteers accept the vaccine, then risk exposure and come down with the disease? That would prove the vaccine ineffective but, in the case of AIDS, could prove fatal. Says Dr. Michael Cairns of the Duke Medical Center in Durham, N.C.: "You can't arbitrarily expose a group of people to a virus to see if the vaccine is protective." Moreover, the behavior of the AIDS virus is so complex and unpredictable that a vaccine based on a derivative of the virus could itself be dangerous.

Last year, nonetheless, a French team under Dr. Daniel Zagury apparently tried, without prior tests on animals, a vaccine on African prostitutes. Many of his colleagues were fearful that he might be experimenting with Third World subjects who had little understanding of the risks involved. Zagury retorted that his critics have "no competence" to judge his methods, but so far has not released or published his results.

As physicians ponder the issues raised by AIDS drug and vaccine testing, Dr. Jean Bernard, 79, chairman on medical ethics of France's Consultative Committee for Life Sciences and Health, urges them to take the long view. He reminds colleagues of the tremendous pressures 30 years ago to cut corners to get a polio vaccine. But, he notes, thousands of lives were saved when researchers took the time to get it right. "The point is," he sums up, "that you have to avoid passion. You must follow normal procedures."

With reporting by B.J. Phillips/Paris, with other bureaus