. The long-term goal of this proposal is to determine whether administration of anti-human immunodeficiency virus (HIV) drugs, specifically dideoxynucleosides (ddNs), to HIV-infected pregnant women will protect the fetus from HIV infection or retard the onset and course of acquired immunodeficiency syndrome (AIDS) in their infected infants. The investigators propose to study the effect of the following ddNs: (1) azidothymidine (AZT), (2) dideoxycytidine (ddC), (3) dideoxyinosine (ddI), and (4) didehydro-dideoxythymidine (D4T) on human placenta structure and function. In addition, they will determine the effects of these ddNs on placenta cell metabolism and function in vitro, using the dissociated placenta cell cultures. Primary cultures of throphoblast and Hofbauer (placental macrophages) cells will be used for in vitro studies because (1) throphoblasts are metabolically the most active cells involved in maintaining pregnancy, and (2) Hofbauer cells, which express CD-4 molecules (the receptor to HIV antigen gp-120) have been implicated in the maternal-fetal transmission of HIV. A systematic approach involving in vitro and in vivo exposure studies will be used to determine whether the in vitro results may be used to predict in vivo outcome. The investigators propose to establish Macaca nemestrina as a nonhuman primate model by performing the above in vitro and in vivo studies with the macaque placenta. If the effects of ddNs on macaque placenta are representative of the effects of ddNs on human placenta, macaque placenta could be used as a preliminary screen to determine the toxicity of new ddNs to the human placenta.
