The search for the cellular reservoirs which maintain human immunodeficiency virus (HIV) in the presence of suppressive antiretroviral therapy (sART) is an ongoing process and necessary to create eradication strategies. In spite of maintaining proviral HIV DNA, circulating T-cells are not the main source of residual viremia during sART nor are they the main source of rebound viremia when sART is interrupted. Although the infection of tissue-associated macrophages has been established as critical to the transmission, maintenance and progress of HIV-disease, little is known as to the degree to which macrophages remain infected or become infected during sART. Their role as a reservoir needs to better elucidated. A primary reason for the paucity of research in macrophages from HIV-infected humans is, being associated with tissues, macrophages must generally be obtained by invasive biopsy. This has led to many studies looking at macrophages derived in culture from monocytes. The placenta is a de novo growth tissue rich in macrophages. It is discarded at birth and therefore provides a unique tissue source to study macrophage infection. We intend to analyze macrophages obtained from placenta at birth from HIV-infected women undergoing sART, comparing their viral forms to those forms in residual viremia. We will also co-culture the infected cells to establish that the virus is viable. We hypothesize these macrophages will harbor a similar virus as that in residual viremia demonstrating that macrophages are the proximal source for the virus during sART.

SC3GM088032

2009-09-01

2019-05-31