The increasing numbers of infants that are infected by HIV-1 infection necessitates the design of effective intervention strategies. However, it will first be necessary to develop and evaluate sensitive methods to detect HIV-1 infection in newborns at birth or shortly after. In addition, more definitive information is needed regarding the role of breast milk, maternal viral load, and maternal and infant HIV-1 neutralizing antibody in the vertical transmission of HIV-1. This study will evaluate a number of different assays performed on specimens from two existing Ugandan cohorts consisting of approximately 775 HIV-1 antibody positive and 225 HIV- antibody negative maternal-infant pairs. The proposed study has the following specific aims: 1. Determine whether the maternal viral burden and/or serum beta-2 microglobulin correlate with HIV-1 vertical transmission and clinical outcome of the infant using the following assays: quantitative total serum HIV-1 P24 antigen, quantitative HIV-1 PCR, serum beta-2 microglobulin. 2. Determine the relationship of the maternal and infant humoral immune response to viral isolates prevalent in the population and in specific maternal-infant pairs using a viral isolate neutralization assay and gp120 V3 loop antibody assays. 3. Determine the sensitivity/specificity of several laboratory assays [HIV- 1 p24 antigen (free and dissociated, HIV-1 culture, HIV-1 PCR, HIV-1 IgA antibody and assay) and clinical assays (BCG scar and PPD induration) to detect HIV-1 infection and predict clinical outcome in the newborns of infected mothers. 4. Determine the role of breast milk in HIV-1 transmission by correlating presence of detectable HIV-1 in breast milk and transmission. These investigations may yield important advances in early detection of HIV-1 and in understanding the role of immunity in HIV-1 vertical transmission. This health related project will also enhance the potential of Uganda as a site for vaccine and chemotherapy trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI032395-01
Application #
3147441
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1991-09-30
Project End
1994-08-31
Budget Start
1991-09-30
Budget End
1992-08-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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
Guay, L A; Hom, D L; Kabengera, S R et al. (2000) HIV-1 ICD p24 antigen detection in ugandan infants: use in early diagnosis of infection and as a marker of disease progression. J Med Virol 62:426-34
Guay, L A; Hom, D L; Mmiro, F et al. (1996) Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission. Pediatrics 98:438-44
Grant, R M; Piwowar, E M; Katongole-Mbidde, E et al. (1996) Comparison of saliva and serum for human immunodeficiency virus type 1 antibody testing in Uganda using a rapid recombinant assay. Clin Diagn Lab Immunol 3:640-4
Jackson, J B; Hom, D; Piwowar, E et al. (1996) Maternal HIV-1 RNA serum levels at delivery and vertical transmission in Uganda. Pediatr AIDS HIV Infect 7:37-42
Tugume, S B; Piwowar, E M; Lutalo, T et al. (1995) Hematological reference ranges among healthy Ugandans. Clin Diagn Lab Immunol 2:233-5
Piwowar, E M; Tugume, S B; Grant, R M et al. (1995) beta-2 Microglobulin values among human immunodeficiency virus (HIV)-negative, HIV-positive asymptomatic, and HIV-positive symptomatic Ugandans. Clin Diagn Lab Immunol 2:236-7
Kabengera, S; Hom, D; Jackson, B (1994) Effect of specimen storage on absolute CD4 counts. Clin Diagn Lab Immunol 1:232-4
Landay, A; Ho, J L; Hom, D et al. (1993) A rapid manual method for CD4+ T-cell quantitation for use in developing countries. AIDS 7:1565-8
Jackson, J B; Kataaha, P; Hom, D L et al. (1993) Beta 2-microglobulin, HIV-1 p24 antibody and acid-dissociated HIV-1 p24 antigen levels: predictive markers for vertical transmission of HIV-1 in pregnant Ugandan women. AIDS 7:1475-9