Infants exposed to HIV- I in utero, intrapartum and through breastfeeding may escape HIV- 1 infection by their ability to mount an immune response. Protective immunity in the HIV-1 exposed infant may be due to a combination of cellular, humoral, genetic, and innate immune mechanisms. To investigate this hypothesis, the proposed study will determine the effect of selected infant immune responses (HIV- 1 specific T-helper responses, salivary HIV- I specific IgA, salivary secretory leukocyte protease inhibitor [SLPIJ) on risk of HIV-l mother-to-child transmission. The study will also characterize factors associated with acquisition of these immune responses and define the association between HIV-l specific CD4+ T-helper responses, cytotoxic T-lymphocyte (CTL) activity, and mucosal antibody production. The proposed study will use an established perinatal cohort in Nairobi, Kenya. HIV-l seropositive pregnant women are recruited at 32 weeks' gestation, counseled about breastfeeding risks of HIV-l transmission, and provided with perinatal zidovudine. During 12 months of postpartum follow-up, blood specimens are collected from infants at birth, 1, 3, 6, 9, and 12 months and assayed for HIV-1 specific CTL activity. In the proposed study, after pilot studies are conducted to optimize field and laboratory procedures, three additional assays will be performed: cord blood PBMCs will be assayed for HIV-l specific CD4+ T-helper responses and saliva will be tested for the presence of HIV-l. gpI6O-specific IgA and SLPI. The study is ideal for the principal investigator, Dr. Farquhar, who plans to pursue a career in epidemiological research that focuses on immunology and HIV- 1. Dr. Farquhar will broaden her research experience in Nairobi by supervising the clinical, laboratory, and data components of the proposed study and three pilot studies. She will also strengthen her skills and knowledge in epidemiology and immunology through formal training at the University of Washington, culminating in a PhD degree in epidemiology. In addition, to complement immunology courses at the University of Washington, Dr. Farquhar will spend three months at Oxford University under the guidance of Dr. Rowland-Jones. This educational program, combined with the mentorship of Drs. Kreiss and John, will prepare her for the complex data analysis required by this study and contribute substantially to the development of her career as an independent clinical investigator.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD041879-03
Application #
6735697
Study Section
Special Emphasis Panel (ZHD1-DRG-A (04))
Program Officer
Ryan, Kevin W
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
3
Fiscal Year
2004
Total Cost
$125,820
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Farquhar, Carey; Wamalwa, Dalton; Selig, Sara et al. (2009) Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre- and post-highly active antiretroviral therapy and revaccination. Pediatr Infect Dis J 28:295-9

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