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.
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