The long-term objectives of the proposed project is to test the hypothesis that administration of zidovudine (ZDV) to HIV positive pregnant women may either reduce the incidence of maternal-fetal HIV transmission or retard the onset and course of AIDS in the offspring. Before this hypothesis can be tested, studies in a representative animal model need to be conducted to ascertain if zidovudine is toxic to the fetus.
The specific aim of this project, therefore, is to determine whether zidovudine (ZDV) is toxic to the fetus in Macaca nemestrina. Maternal-fetal transmission of HIV is an increasingly important contributor to the incidence of AIDS in the pediatric population. Currently, administration of ZDV to a pregnant woman with HIV infection is not recommended since the toxicity of ZDV to the fetus is not known. Despite this lack of information, the need to treat this patient population has become so urgent that a clinical trial in which ZDV is to be administered to HIV positive pregnant women during the third trimester has recently been approved. The present proposal, therefore, seeks to examine the fetal toxicity of ZDV in a representative animal model, the macaque, when ZDV is administered throughout the gestational period. Twelve time-mated healthy macaques (M. nemestrina) will be administered either ZDV (test animals; 20mg q4h orally) or water (control animals), via a gastric catheter, prior to conception and during the entire gestational period. The physical, clinical, neurological, perceptual, motor and social development of the offspring will be measured and compared between the two groups: test and control. The use of healthy dams rather than those infected with an immunodeficiency virus will allow determination of the fetal toxicity (if any) of ZDV without confounding factors such as fetal toxicity of the immunodeficiency virus. The studies proposed here should yield useful information on the fetal toxicity of ZDV. In addition, the execution of the proposed studies will result in the development of an animal model to test the fetal toxicity of future anti-HIV drugs, in particular the newer dideoxynucleosides.
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