WHAT ABOUT THE KIDS?

By Christine Gorman

Actor and director Paul Glaser has faced bad news before. Eleven years ago, he and his wife Elizabeth learned that she had been infected with HIV during a blood transfusion and had unknowingly passed the infection on to their two children, Ariel and Jake. Since then both Glaser's wife and his daughter have died. So he wasn't altogether surprised when doctors told him in November that the levels of HIV in Jake's blood had started to climb--a sign that the 12-year-old's immune system was beginning to fail. But neither was Glaser totally prepared for what happened next.

Jake's doctors wanted to put the boy on protease inhibitors, the breakthrough new anti-HIV medications that, in combination with other antiviral drugs, have so dramatically changed the lives of tens of thousands of adults with AIDS over the past year. The Food and Drug Administration, however, hadn't yet approved the drugs for use in children, so no one knew how well the treatment would work. Furthermore, since children metabolize drugs more quickly than adults, physicians could only guess at the proper dosage. Too much could kill Jake. Too little might inadvertently create a mutant strain of the virus that could defy future treatment.

Undaunted, Glaser decided to take the chance that might save his only remaining child. "If you're drowning in a river, and someone throws you something that looks like it will float and looks like it might not, you're still going to grab onto it--aren't you?" he asks. Glaser's gamble seems to have paid off. Within two weeks of starting treatment, Jake's viral count had dropped below his doctors' ability to measure it.

When it comes to treating children with HIV and AIDS, physicians are often forced to practice hand-me-down medicine. There are 275,000 adults living with HIV in the U.S. and only 4,500 HIV-positive youngsters under age 13--most of whom were infected in the womb. Children are not just smaller, cuter copies of adults. Their immune systems are not yet fully developed. Their brains are more vulnerable to HIV. When they get sick with AIDS, many of them deteriorate more rapidly than adults. They need treatments tailored to their size and condition. "But pharmaceutical companies do not perceive pediatric drugs as a huge market share," says Glaser, chairman of the Pediatric AIDS Foundation co-founded by his wife with two of her friends in 1988. "They're not going to spend a lot of time and money on it unless we give them the incentive to do so."

They got some incentive two weeks ago, when the FDA approved for the first time the use of two protease inhibitors for children--Agouron's nelfinavir and Abbott's ritonavir. But parents and pediatricians complain that they still don't have enough information about how to use them. Nelfinavir, in particular, "went through the approval process very rapidly," says Dr. Mark Kline, associate professor of pediatrics at Baylor College of Medicine in Houston. "There are some basic pieces of information about nelfinavir that we don't have--like how often to give the drug or in what dose."

Frustrated doctors have resorted to performing their own clinical trials. Kline recalls attending the international AIDS conference in Vancouver, Canada, last July and being overwhelmed by the flood of reports detailing how well various protease inhibitors were working on adults. "I couldn't in good conscience come back to Houston and take care of 300 kids with HIV and keep telling families that we couldn't offer protease inhibitors because we didn't know the correct dose," he remembers thinking. So Kline designed a simple study of 20 kids, ages 4 to 12, and made an educated guess at a dose that might be strong enough to do some good without doing irreparable harm. "The companies have not generated these data," he says. "I'm doing it here, and someone else is doing it at St. Jude's, and someone else is doing it in California. It certainly isn't a very efficient way of getting the information out."

Unfortunately, that kind of piecemeal progress has long been part of the territory in treating pediatric AIDS. AZT, the first drug shown to fight AIDS, wasn't okayed for children until 1990--three years after it had been approved for adults. The syrup form, which is easier for children to swallow, didn't become available until 1989.

Such delays can prove fatal. Tanya (not her real name), an 11-year-old from Miami who is HIV positive, had to watch her younger sister die last year while they waited for permission to take a protease inhibitor. Both girls had been infected in utero; their mother died a couple of years later. "The [pharmaceutical company] said they didn't have the right dosage for children," the girls' foster mother recalls. "They told us to hold out. But by the time she got accepted, it was too late [for Tanya's sister]." In February, Tanya started combination therapy with ritonavir and has since added seven pounds to her 75-lb. frame. The popular sixth-grader now feels well enough to have sleepovers at a friend's house and go on school field trips.

While they wait for the government and the drug companies to act, doctors and nurses have developed ingenious tricks to dilute adult-strength AIDS drugs and get them into kids. In some cases they chop up the capsules and mix the medication with applesauce or baby formula. But mashed up protease inhibitors taste so bitter that most kids just spit them out. So doctors are teaching children as young as 2 how to swallow the intact capsules.

But just because they can get protease inhibitors into their youngest patients doesn't mean that pediatricians are eager to do so. With children as with adults, patients' first response to a protease inhibitor is often their best. If they take the drug too soon, the HIV in their body can become resistant not only to that particular drug but to the whole family of protease inhibitors. As a result, most doctors will give the drugs only to those children who are clearly deteriorating.

Still, pediatricians are following the experiments of AIDS pioneer Dr. David Ho with great interest. Ho believes that doctors must hit HIV early and hard if they ever hope to clear the virus from the body. If the current generation of protease inhibitors, or new ones being developed, are successful in vanquishing HIV in adults, then pediatricians may consider using a similar approach with newborns. But they would need a lot more safety data before they could even attempt such an experiment. For one thing, babies' livers are too immature to process the powerful drugs. A full-strength dose might kill a toddler.

A more likely next step, therefore, would be to place pregnant women who are HIV positive on a combination of protease inhibitors and AZT. About 1 in 4 children born to untreated HIV-positive mothers develop the infection themselves. The use of AZT during pregnancy has cut that transmission rate to 8%. In the next few months researchers will begin putting HIV-infected mothers on combination therapy with protease inhibitors to see if they can cut the rate to zero. But protease inhibitors are so much more powerful and potentially toxic than AZT that no one knows what harm it might do to the developing fetus.

Much has been accomplished, but even more remains to be done. Fifteen years ago, children infected with HIV lived an average of 18 months. Today many are teenagers, dreaming about first dates and proms and even law school. "We're no longer content to buy another year or two," says Dr. Joseph Church of Childrens Hospital Los Angeles. Nowadays, doctors think they might even have a chance to see their young patients grow up.

--Reported by Tammerlin Drummond/Miami and Alice Park and Victoria Rainert/New York

With reporting by TAMMERLIN DRUMMOND/MIAMI AND ALICE PARK AND VICTORIA RAINERT/NEW YORK