HIV immune environment impact on pre-eclampsia

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PROJECT SUMMARY/ABSTRACT Pre-eclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality. It is a placental-driven disease characterized by alterations in placental development and placental perfusion that lead to the clinical stage of placental oxidative stress, hypertension and proteinuria. The exact etiology of PE is still unknown. However, a growing body of evidence suggests that immune imbalances during placentation may drive the development of the disease. In particular, PE seems to be characterized by a lack of Th1/Th2 switch early after conception and an altered immune and angiogenic environment with higher levels of inflammatory markers and lower levels of tolerogenic markers. Moreover, impaired phenotype and function of decidual NK cells, which play a critical role in placentation, are probably involved interfering with correct trophoblast invasion. HIV infection in untreated pregnant women appears to drive lower rates of PE development. This may be due to HIV-driven immune suppression. However, HIV infected women treated with combination antiretroviral therapy (cART) may be at higher risk of PE than untreated women or uninfected controls. The exact impact of cART on the development of PE is still unclear. However, studies that distinguish cART at conception from cART started during the 2nd or 3rd trimester report higher incidence of PE in women treated with cART at conception. Herein we will test the hypothesis that immune imbalances in HIV infected pregnant women treated with cART at conception predispose to the development of PE. We will test our hypothesis investigating samples collected from a large, concluded IMPAACT study, P1025. The P1025 study samples will allow for the comparison of 2nd and early 3rd trimester women on cART at conception with HIV infected women who started cART during the 2nd trimester. Our two specific aims focus on: SA1) determining the association of cART at conception with known angiogenic and inflammatory markers of PE and, SA2) investigating if and how immune cell markers on T cell and NK cell subsets correlate with angiogenic markers that are known to predict the development of PE in women on cART at conception. In conclusion, we are addressing a critical problem in maternal health in HIV infected women that could help to identify and test new strategies to reduce the development of PE in cART-treated HIV infected pregnant women.