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.

Public Health Relevance

In order to create strategies to eradicate human immunodeficiency virus infection from within an individual, it is necessary to identify the cells i which the virus is maintained during ongoing antiretroviral therapy. Tissue macrophages are a likely source. This study will determine whether placenta-associated tissue macrophages maintain and produce infectious virus over the course of long-term antiretroviral therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
5SC3GM088032-08
Application #
9276009
Study Section
HIV/AIDS Vaccines Study Study Section (VACC)
Program Officer
Krasnewich, Donna M
Project Start
2009-09-01
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
8
Fiscal Year
2017
Total Cost
$108,738
Indirect Cost
$41,238
Name
Ponce School of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
105742043
City
Ponce
State
PR
Country
United States
Zip Code
00732