Hoping that two drugs are better than one, researchers studying AIDS in children now are using combinations of medicines that singly have shown they can slow progress of the incurable, fatal disease, a Johns Hopkins pediatric infectious disease investigator says.
Dr. John F. Modlin said yesterday that one of the newest trials involving Hopkins patients is a multicenter study of 250 children using zidovudine, commonly called AZT, and intravenous immunoglobulin, an immune boosting drug. For comparison, another group of children is receiving AZT and a placebo.
"We're hoping these kids will do better when we give them two drugs that have been effective," he said. "We're practicing adjuvant therapy, the kind that has worked so successfully for cancer patients. The battle against acquired immune deficiency syndrome will be won in small bits and chunks -- there will be no one certain dose and no one perfect drug."
The AZT-intravenous immunoglobulin study is just one of "lots of studies like this," Modlin said. About 35 pediatric centers are now part of the federally funded AIDS Clinical Trials Group, which is conducting much of this research.
To date, about 3,000 cases of AIDS among children under age 13 have been reported to the federal Centers for Disease Control. Most of these youngsters got the virus from their mothers as babies, the CDC said. The problem of AIDS among children is expected to grow due to the increasing number of women with AIDS.
The AZT-intravenous immunoglobulin study is expected to go on for another two years unless the researchers stumble on some dramatic finding that cuts it short.
This is exactly what happened in January when intravenous immunoglobulin proved successful in fending off deadly infections that often kill children with AIDS symptoms.
The results of a nationwide study of 372 children were so impressive that study officials stopped the trial and immediately started giving the therapy to those children in the study who had been receiving phony infusions for comparison purposes.
The children who received the treatment monthly went more than 19 months before developing their first AIDS-related infection, compared with a little more than seven months for those receiving phony infusions.
The treatment also resulted in fewer hospitalizations for the children, who ranged from six months to 12 years old. Only about one percent of the youngsters suffered adverse reactions from the drug, the researchers said.
"This therapy joins AZT as a drug of choice for treating pediatric AIDS patients," Dr. William Shearer, director of the study and professor of pediatrics at Baylor College of Medicine in Houston, said at the time.
Modlin was one of the investigators in a multicenter, landmark study of AZT in children, published in today's New England Journal of Medicine, which prompted the U.S. Food and Drug Administration last year to approve the drug's widespread use. That approval came three years after trials had shown AZT was effective in adults.
Nine of the 88 children who were enrolled in the AZT study were Hopkins patients. Of the nine, six are still alive. All are on higher doses of AZT than are currently being used in adult AIDS patients, according to Modlin.
This is the standard therapy for children with symptomatic or advanced AIDS, who are at high risk for infection and death, now that the study has found the dosage is safe and well-tolerated.
The amount of a strawberry-flavored syrup preparation of AZT given depends on a child's size. An average-size 2 1/2 -year-old child would get about two teaspoonsful every six hours, according to Modlin.
"Although the study design was not the most rigorous, the investigators had a strong impression that AZT improves survival," Modlin said.
AZT therapy also was associated with a substantial improvement in weight gain.