Case Western Reserve University, Nakasero Blood Bank, Makerere University, the National Bacteriological Laboratory of Sweden and the Ugandan Ministry of Health propose to prepare and test an HIV-1 hyperimmune intravenous immune globulin (HIVIG) in phase I/II and III trials for the prevention of HIV-1 vertical transmission from HIV-1 infected pregnant Ugandan women to their neonates. The investigators of this proposal recently received funding from the World Health Organization to collect and process enough HIV-1 seropositive plasma for a potential Phase I/II and III HIVIG trial in pregnant Ugandan women. This NIH application seeks funding to conduct phase I/II and III trials of HIVIG and to prepare the HIVIG preparation for the phase III trial.
SPECIFIC AIMS are to perform the following: Phase I/II Trial 1. Evaluate the safety and tolerance of HIVIG in a two arm trial in which 10 mother-infant pairs per arm receive HIVIG (100 mg/kg or 200 mg/kg) at 37-38 weeks gestation and within 16 hours of birth (infant only). 2. Generate data on the titer of neutralizing and V3 loop antibodies to HIV-1 in mothers treated with HIVIG. 3. Determine whether a decrease in viral load and improvements in immunological parameters occur in mothers treated with HIVIG at the two different doses during the intrapartum period. 4. Determine the preliminary rate of HIV-1 vertical transmission in the maternal-infant pairs receiving HIVIG using laboratory detection methods for the early diagnosis of HIV-1 infection. Assuming adequate safety and tolerance, the dose of HIVIG for a phase III trial will be based on data generated in aims 2, 3, and 4. Phase III Trial 1. Determine the efficacy of HIVIG versus intravenous immune globulin (IVIG) in a two arm (200 mother-infant pairs per arm) randomized controlled trial to significantly decrease the HIV-1 vertical transmission rate as detected by Western blot at 15 months of age or two positive HIV-1 cultures or DNA PCR assays on different specimens collected at birth, 6 weeks, 14 weeks, and 6 months of age. 2. Evaluate the differences in clinical progression to AIDS, the decline in CD4 counts, and survival at 2.5 years in the HIV-1 infected infants who received HIVIG or IVIG.
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