Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI034235-06S1
Application #
6800598
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Sharma, Usha K
Project Start
1993-09-01
Project End
2005-03-31
Budget Start
1998-04-01
Budget End
2005-03-31
Support Year
6
Fiscal Year
2003
Total Cost
$1,500,001
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Onyango-Makumbi, Carolyne; Omer, Saad B; Mubiru, Michael et al. (2011) Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY). J Acquir Immune Defic Syndr 58:399-407
Onyango-Makumbi, Carolyne; Bagenda, Danstan; Mwatha, Antony et al. (2010) Early weaning of HIV-exposed uninfected infants and risk of serious gastroenteritis: Findings from two perinatal HIV prevention trials in Kampala, Uganda. J Acquir Immune Defic Syndr 53:20-7
Church, Jessica D; Huang, Wei; Mwatha, Anthony et al. (2010) Analysis of HIV tropism in Ugandan infants. Curr HIV Res 8:498-503
Heaton, R K; Clifford, D B; Franklin Jr, D R et al. (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087-96
Church, Jessica D; Mwatha, Anthony; Bagenda, Danstan et al. (2009) In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. AIDS Res Hum Retroviruses 25:673-7
Church, Jessica D; Huang, Wei; Parkin, Neil et al. (2009) Comparison of laboratory methods for analysis of non-nucleoside reverse transcriptase inhibitor resistance in Ugandan infants. AIDS Res Hum Retroviruses 25:657-63
Church, Jessica D; Omer, Saad B; Guay, Laura A et al. (2008) Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. J Infect Dis 198:1075-82
Six Week Extended-Dose Nevirapine (SWEN) Study Team; Bedri, Abubaker; Gudetta, Berhanu et al. (2008) Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet 372:300-13
Guay, Laura A; Musoke, Philippa; Hom, David L et al. (2002) Phase I/II trial of HIV-1 hyperimmune globulin for the prevention of HIV-1 vertical transmission in Uganda. AIDS 16:1391-400
Mellquist, J L; Bowman, B; Kasturi, L et al. (1998) Characterization of HIV type 1 gp120 V3 region sequences from Ugandan infants. AIDS Res Hum Retroviruses 14:1391-5

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