Children with AIDS

by Food and Drug Administration (FDA)

Betty's eyes well with tears when she speaks of her 3-year-old daughter who has AIDS. "Sometimes I put my face next to her at night to see if she's breathing. If I hear nothing, I touch her. When she moves, I'm relieved."

Betty (not her real name), who also has AIDS, continues, "AIDS has changed my whole life. My husband knew he had the disease, but didn't tell me. It's all right if he gave it to me, but not to my daughter. I'm trying to be strong for her, to live for her. But I want her to live for me."

Approximately 30 percent of infants born to mothers who are infected with the human immunodeficiency virus (HIV) that causes AIDS are also infected with the virus. Nearly 72 percent of the mothers are or have been drug abusers, or acquired HIV infection from sex partners who were IV drug users, as is the case with Betty. The mother often has no detectable signs or symptoms of the disease yet, but is still capable of transmitting it to her infant before or during birth.

Children may also acquire the infection after birth from breast milk contaminated with the virus, which is rare, or from the transfusion of contaminated blood products, although current testing of all blood donors makes this very unlikely.

According to the U.S. Centers for Disease Control, there were 2,315 children younger than 13 in the United States with reported acquired immune deficiency syndrome (AIDS), the most severe form of HIV infection, by the end of May 1990. This is more than double the number of cumulative AIDS cases reported as of the end of July 1988. Fifty-two percent of these children are black, and a quarter are Hispanic.

This does not include those who are HIV-infected but have no symptoms, nor those who have symptomatic HIV infection. Conservative estimates project that there will be nearly 20,000 children in the United States infected with HIV by 1991.

Rapid Progression

Barring a cure, many of these children are expected to die an agonizing death. AIDS in infants progresses much more rapidly than in adults. According to CDC, the average age of diagnosis of AIDS in infants is 9 months. Often, they die shortly thereafter.

Because the impact of AIDS in children is complicated by the immaturity of their immune systems, those children who do survive the first two years of life often require repeated hospitalizations for bacterial infections, recurrent pneumonia, fevers, and weight loss.

One of the major problems of treating AIDS is that the virus (a retrovirus) incorporates its genetic material into the DNA, or genetic material, of the infected person. Once incorporated, a person's cells then become a factory for making more virus, which is then released and can go on to infect other cells.

According to Philip Pizzo, M.D., chief, pediatric branch and infectious diseases section, National Cancer Institute (NCI), "We're unlikely to have a curative therapy unless we can get the virus out of the cell, or destroy all of the cells the virus has infected."

But any treatment that could destroy the virus's DNA could destroy the infected person's DNA as well. So, in the meantime, Pizzo says investigators are trying to find ways to suppress the infection.

He says that the goal is to build on the principles of treatment already developed for other diseases, such as pediatric cancer. In recent years, the multidisciplinary treatment given pediatric cancer patients has resulted in their longer survival.

As in cancer therapy, Pizzo hopes that by treating AIDS patients with a combination of medications, physicians will be able to target the several body organs affected by the disease and reduce the toxicity of any one drug.

"The mental framework I work in is that, like cancer, we hope to one day be able to put AIDS into remission," said Pizzo.

Toward that goal, numerous clinical trials with children using anti-retroviral agents have been undertaken in the pediatric branch of NCI and under the auspices of the National Institute of Allergy and Infectious Diseases (NIAID) AIDS Clinical Trials Group (ACTG).

AZT for Children

In May 1990, as a result of these trials, zidovudine (commonly called AZT) was the first drug approved for children with symptomatic HIV infection or AIDS. AZT was first approved in adult AIDS patients in 1987 after it had been shown to extend their lives by slowing the progress of the disease.

In giving its approval for use of AZT in children, the Food and Drug Administration attempted to act swiftly by not requiring the effectiveness of AZT to be fully evaluated in children after its effectiveness was demonstrated in adults and its safety in children was documented.

According to Ellen Cooper, M.D., director of FDA's division of antiviral drug products, "In life-threatening diseases like AIDS, we always have more flexibility. We're always willing to take more risks. We waived the regulation that requires well-controlled studies in children, as well as in adults, for labeling of a drug for use in children. Instead, we depended on well-controlled trials of AZT in adults. In this way, we were able to approve AZT for children more quickly."

According to James Bilstad, M.D., director of FDA's office of drug evaluation II, until recently, "children were therapeutic orphans. In the past, we've treated the use of adult drugs in pediatrics as a separate indication that needed adequate and well-controlled studies for approval. But in many cases, such as AIDS, we feel we can consider the pediatric population an extension of the patient population for drug approval purposes. To do adequate, well-controlled studies is a major undertaking and takes a long time. If we have less information, it's OK. We can still get pediatric safety and dosage information without a controlled study."

But while AZT has extended the lives of people with AIDS, it also can inhibit the production of red blood cells, which are necessary for oxygen transport. It may also reduce the number of white blood cells, an important part of the body's defense mechanism against infection. Also, over time, the AIDS virus may develop a resistance to AZT.

Therefore, researchers in private industry, in academia, and at the National Institutes of Health are evaluating other drugs chemically related to AZT, such as DDC (dideoxycytidine) and DDI (dideoxyinosine). In keeping with the efforts to get medications for AIDS quickly to children, studies in children often begin shortly after those in adults.

Questions remain, however, about the drugs' effectiveness and proper role in treatment: whether they would be best used as a backup to AZT, an alternative to AZT, or in combination with AZT.

Other clinical studies are under way to determine whether intravenous immunoglobulin or antibody therapy might decrease the number of bacterial infections that occur in children infected with HIV.

Another therapy now in pediatric trials is recombinant CD4, which may interrupt the life cycle of HIV by preventing the attachment of the virus to cells.

About the Author

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