Abstract

Approximately 500,000 HIV-infected children are born each year in sub-Saharan Africa. Nevirapine treatment programs could prevent about half of these infections. In Arica, maternal malaria is common and frequently causes low birth weight. Important interactions between HIV and malaria infections in pregnant women have been identified ane low-cost interventions to prevent maternal materia are known. The current proposal aims to test the following hypotheses: 1. Maternal malaria increases mother-to-child transmission (MTCT) of HIV in nevirapine-treated women and children; malaria may have this effect by increasing maternal viral load, placental monocytes, and placental concentrations of TNF-alpha and CCR5; and 2. HIV-1 infections inhibit the development of pregnancy-specific anti-malarial immunity and exacerbates maternal malaria. To test these hypotheses, we will enroll approximately 1400 women at antenatal clinics in Blantyre, Malawi. HIV-positive women and their offspring will be treated with nevirapine. 400 HIV-positive women will be enrolled in a prospective cohort study in which the effects of maternal malaria. To test these hypotheses, we will enroll approximately 1400 women at antenatal clinics in Blantyre, Malawi. HIV-positive women and their offspring will be treated with nevirapine. 400 HIV-positive women will be enrolled in a prospective cohort study in which the effects of maternal malaria on HIV transmission rates will be determined. In this same group of women, we will investigate how malaria affects maternal peripheral and placental viral loads, placental histopathology, and placental and cord blood cytokine and chemokine levels. In a second substudy, the effects of HIV on pregnancy-specific antimalarial immunity (antibodies to chondroitin sulfate. A binding infected erythrocytes) will be assessed in 4 groups of 52 multigrivida (HIV+/malaria+, HIV+/malaria-). The results of this study will have important implications for designing public health program s for antenatal care in African and should promote our understanding of the pathogenesis of MTCT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049084-06
Application #
6862582
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Sharma, Usha K
Project Start
2001-03-15
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2007-02-28
Support Year
6
Fiscal Year
2005
Total Cost
$278,387
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Munroe, Melissa E; Lu, Rufei; Zhao, Yan D et al. (2016) Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis 75:2014-2021
Mates, Jessica M; Kumar, Surender B; Bazan, Jose et al. (2014) Genotypic and phenotypic heterogeneity in the U3R region of HIV type 1 subtype C. AIDS Res Hum Retroviruses 30:102-12
Turner, Abigail Norris; Tabbah, Sammy; Mwapasa, Victor et al. (2013) Severity of maternal HIV-1 disease is associated with adverse birth outcomes in Malawian women: a cohort study. J Acquir Immune Defic Syndr 64:392-9
Kumar, Surender B; Rice, Cara E; Milner Jr, Danny A et al. (2012) Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission. AIDS 26:685-94
Taylor, Steve M; Antonia, Alejandro; Feng, Gaoqian et al. (2012) Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study. Infect Genet Evol 12:282-90
Taylor, Steve M; Antonia, Alejandro L; Chaluluka, Ebbie et al. (2012) Antenatal receipt of sulfadoxine-pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study. Clin Infect Dis 55:42-50
Russell, Elizabeth S; Kwiek, Jesse J; Keys, Jessica et al. (2011) The genetic bottleneck in vertical transmission of subtype C HIV-1 is not driven by selection of especially neutralization-resistant virus from the maternal viral population. J Virol 85:8253-62
Ataide, Ricardo; Mwapasa, Victor; Molyneux, Malcolm E et al. (2011) Antibodies that induce phagocytosis of malaria infected erythrocytes: effect of HIV infection and correlation with clinical outcomes. PLoS One 6:e22491
Kumar, Surender B; Handelman, Samuel K; Voronkin, Igor et al. (2011) Different regions of HIV-1 subtype C env are associated with placental localization and in utero mother-to-child transmission. J Virol 85:7142-52
Ataide, Ricardo; Hasang, Wina; Wilson, Danny W et al. (2010) Using an improved phagocytosis assay to evaluate the effect of HIV on specific antibodies to pregnancy-associated malaria. PLoS One 5:e10807

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