June 23, 1999 GAINESVILLE, Fla.---Young children infected with HIV have one substantial advantage over those who are older: a much greater capacity for immune system restoration when treated with a potent new class of AIDS drugs, according to a new University of Florida study.
In about two-thirds of the 44 children in the study, the number of T cells, an indicator of immune functioning, increased to normal levels. Children under 6 showed the most pronounced improvement.
"Their immune systems came back very dramatically and to a much greater extent than would have been expected based on the earlier trials done with adults," said Dr. John W. Sleasman, chief of pediatric immunology and infectious diseases in UF's College of Medicine, whose article on the study was published in last month's Journal of Pediatrics.
"We have now followed these children for more than two years, and many of them continue to do extremely well," said Sleasman, noting that some who had been quite sick are spending much less time in the hospital, have suffered fewer illnesses and are able to attend school regularly.
"The hope is that this will be a long-lasting and durable immune reconstitution," he said.
Sleasman's analysis is based on data collected during the first U.S. clinical trial of children treated with a so-called drug cocktail--a combination of medications that includes a protease inhibitor, the class of drugs shown to interfere effectively in replication of the HIV virus. In the trial - a collaborative effort of the University of Florida, the University of South Florida and the National Cancer Institute -- children were treated with ritonavir, zidovudine and didanosine.
Strong antiretroviral therapy such as the type used in the study now is the standard ongoing treatment for adults and children who can manage the complex regimen and tolerate its side effects. While far from a cure, the medications have been credited for a sharp drop in AIDS deaths in the United States and for allowing people with the disease to live healthier lives.
Most of the research on the medications, however, has been conducted with adult patients. For many of them, the treatment has led to significant drops in what is known as viral load -- the number of copies of the virus found in a blood sample. But studies in adults have shown that it does not typically lead to much repair of immune system damage.
"With adults, the hope is that the medications will stave off further destruction of the immune system," Sleasman said. "But we're seeing a different potential in young children. In children under 5, the thymus gland, which is where T cells mature, is quite large and active. As you get older, it gets smaller, so that by the time you are a teen-ager, it actually atrophies."
This developmental difference appears to help explain why many younger people are able to produce significant numbers of new T cells in response to treatment, Sleasman said. Even some children whose viral load stayed high showed signs of rejuvenation in T cell numbers.
"The therapy is having a dramatic impact on the management of HIV-infected children," Sleasman said. "We're seeing a significant decrease in the number of children who are developing opportunistic infections and other complications of AIDS. We're seeing fewer children admitted to the hospital with pneumonia and other AIDS-defining illnesses."
Before the drug cocktail therapy, Shands at UF medical center, which serves as UF's teaching hospital, used to have two or three children at a time being treated for an AIDS-related problem.
"Now it's a rarity," Sleasman said.
"This was one of the first studies to show that there is hope to reversing some of the immune abnormalities," said Dr. Katherine Luzuriaga, an associate professor of pediatrics at the University of Massachusetts Medical Center, who also researches AIDS in children. "Further studies are looking at newer and even more potent medication regimens and their effects on the immune system. Over the next year or so, we should begin to know the results of these studies."
The Pediatric AIDS Foundation recently awarded Sleasman a $192,000 grant to continue his research. During the next two years, he plans to compare the potential for immune system reconstitution in children under 2, those between 2 and 12, and adolescents.
"We're not only going to look at the numbers of cells that reconstitute following therapy. We're going to look at the ability of cells to function, to see how they respond to some standard vaccinations," he said.
The researchers also will examine whether it would be safe to stop giving children some medications designed to prevent specific illnesses, such as certain types of pneumonia.
"Many of these children have to take 20 to 30 pills a day," he said. "Imagine with a small child how difficult that is. If we can get down the number of medications they take, obviously their quality of life will be better. The potential for side effects will diminish, and compliance with the medication regimen will improve."
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