author's abstract.) The incidence of the acquired immunodeficiency syndrome (AIDS) in children is rapidly increasing as the number of women infected with the human immunodeficiency virus (HIV) is reaching alarming proportions. To understand better the pathophysiology of maternal-fetal transmission of HIV in humans, the Principal Investigator proposes to develop a model of maternal-fetal transmission of SIV in pigtailed macaques (Macaca nemestrina). In preliminary experiments, the research team observed that one of the three offspring born to mothers inoculated with SIV during the latter part of the third trimester became infected. The SIV-infected infant was born 31 days after the mother was inoculated with SIV and became virus positive by culture and polymerase chain reaction (PCR) at one month and symptomatic for simian AIDS (SAIDS) at four months of age. He died at age six and one-half months of disseminated adenovirus infection. The other two infants, born 16 and 25 days following inoculation of the mothers, remained virus negative and are healthy at one year of age. The Investigator proposes, during the next four years, to study maternal-fetal transmission of SIV in 48 pregnant M. nemestrina. During the first two years, the researcher team will modify several aspects of the model to increase the rate of fetal infection to 75% of viable infants. These modifications include inoculation at earlier gestational ages and mild immunosuppression of the mother with low doses of cyclosporin A and depot-medrol. During the second year, the team will conduct experiments to determine the time of transfer of SIV to the fetus. During the third and fourth years, the team will use the model to explore antiviral drugs for their effectiveness in preventing maternal-fetal transmission of SIV. The team will evaluate drugs affecting viral replication (e.g., dideoxynucleoside analogs) as well as viral adhesion (e.g. CD4-IgG). Their goal is to define the model of maternal-fetal transmission of SIV and to explore possibilities that will prevent infection of the offspring. These studies will provide information that can not be obtained by observing HIV-infected women and their offspring.
