The ACTG 076 trial, conducted in the United States and Europe, showed that zidovudine given to the mother during delivery and to the infant for six weeks could reduce HIV mother to child transmission by two-thirds. Because of the high cost and compliance problems, however, including the use of intravenous drug during delivery, the lengthy treatment is not optimal. This study is designed to answer the question of whether the duration of prophylactic ZDV treatment can be reduced without increasing the risk of transmission. The proposed study is a Phase II/III double-blind, randomized, controlled, equivalence trial in which the Principal Investigator and his associates will compare long vs. shortened ZDV regimens on the prevention of HIV-1 mother-to-child transmission. The objectives are to: (1) test the equivalence of shorted ZDV regimens administered to pregnant women and their infants, with a long regime of proven efficacy; (2) assess the safety and tolerance of ZDV in mothers and infants; (3) study the pharmacokinetics of ZDV administered orally to pregnant women during labor and delivery; and )4) study the factors associated with transmission related to maternal health, viral replication, phenotype, genotype, and delivery. The study will be conducted in Thailand (Bankok and norther provinces), as a collaborative effort between Harvard, Mahidol, and Chiang Mai Universities and the Ministry of Public Health of the Kingdom of Thailand. Approximately 1500 mother-child pairs will be enrolled in the study; all eligible women will receive ZDV prophylaxis during pregnancy as will their infants after delivery, in a randomized 2 X 2 factorial design. The women will be randomized at 28 weeks of gestation to receive: (1) prenatal treatment beginning at 28 weeks gestation plus 6 weeks of infant treatment; (2) prenatal treatment beginning at 28 weeks gestation plus 3 to 4 days of infant treatment; (3) prenatal treatment beginning at 34 weeks plus 6 weeks of infant treatment, and (4) a shortened course prenatal treatment at 34 weeks plus 3 to 4 days infant treatment. The primary endpoint is HIV infection in the infant as defined by positive polymerase chain reaction (PCR) on two sequential samples and confirmed by a serology 18 months post delivery. Secondary endpoints include: (1) the timing of transmission in utero as defined by a positive PCR within the first 48 hours; (2) the safety and tolerance of ZDV in the mother and infant and a pharmacodynamic study of oral ZDV. The quantification of maternal viral load, assessment of SCV resistance, and phenotypic characterization of virus isolates will be done in a nested case-control study of 40 mothers of infected infants and 80 mothers of uninfected infants.
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