a SLACK Incorporated newspaper
February 1999
WASHINGTON, D.C. - Children exposed to zidovudine (AZT, Retrovir, Glaxo Wellcome) in utero and as newborns show no cancers or other adverse health effects up through preschool age, according to a recent study in the Journal of the American Medical Association (JAMA).
This is the first report to assess the late effects of AZT exposure in healthy children born to mothers who took the drug to prevent perinatal transmission of HIV. There was concern that these children escaped HIV only to be at risk for cancers.
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The 234 children born without HIV evaluated in this study are part of the Pediatric AIDS Clinical Trials Group (PACTG) 219, a long-term follow-up study that includes more than 2,200 children who have been enrolled in PACTG prevention and treatment protocols.
The 234 children were born to mothers who participated in PACTG 076, the landmark study that showed AZT can reduce by approximately two-thirds HIV transmission from an infected woman to her infant. The children in PACTG 076 were exposed to AZT or a placebo in utero and during labor and delivery, and also as newborns for six weeks. The randomized design of PACTG 076 and subsequent follow-up in this study made it easier to evaluate AZT's potential toxicity, the investigators said. The health of 122 children who received AZT can be compared with that of the 112 children who received placebo.
For the current study, the investigators evaluated the children at regular intervals. The main measures of interest included physical growth, cognitive and developmental milestones, im munologic function, cardiac and ophthalmologic evaluations, the occurrence of malignancies and mortality.
"The good news is that there are no differences in growth and cognitive development between the children exposed to AZT vs. the children who were not," said lead author Mary Culnane, MS, CRNP of the National Institute of Allergy and Infectious Disease (NIAID) pediatric medicine branch in the Division of AIDS. "It is also reassuring that none of the children have developed cancers or died."
The JAMA article reported on data collected through February 1997. The children ranged in age from 3.2 to 5.6 years. They continued to be followed in the PACTG clinics.
The cancer risk was suggested by a National Cancer Institute (NCI) study that suggested very high doses of AZT may induce lung and liver tumors in the offspring of pregnant mice given the drug during the last trimester of pregnancy. The mouse study done in 1997 used study doses that were equivalent to 12 to 50 times the dose used by pregnant women.
The transplacental carcinogenic effect was not seen in a second mouse study performed by Glaxo Wellcome. Glaxo scientists treated pregnant mice with doses of AZT that were higher than those given to humans, but lower than the NCI doses. The Glaxo study did not find an increase in the incidence of tumors in the mothers or their offspring. The study did find an increase in the incidence of vaginal tumors in mice. These tumors appeared to be a result of exposure to the drug present in the urine which comes in contact with vaginal cells.
The authors in the human study concluded that their findings complement the earlier findings of PACTG 076, which found no evidence of AZT toxicity in children up to 18 months of age, and are consistent with earlier limited safety data concerning perinatal exposure to AZT. Future evaluations of these and other children in PACTG 219 will help define the long-term safety of AZT use during the perinatal period. Pediatric HIV specialists also hope to establish a registry to track the health of all children exposed to antiretrovirals, a proposal that is being actively discussed within the medical community.
The study was sponsored by PACTG and funded by NIAID.
For more information:
- Culane M, Fowler MG, Lee SS, et. al. Lack of long-term effects among uninfected children exposed to zidovudine. JAMA. 1999;281:151-57.
- CDC. Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant women infected with HIV-1 for maternal health and for reducing perinatal HIV-1 transmission in the United States. MMWR. 1998;47:2-26.
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