CONTROLLING HIV/SIV WITH DRUGS THAT MANIPULATE LYMPHOCYTE TRAFFICKING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Building upon surprising results obtained in our laboratory in the mouse/LCMV model, this project is designed to test the ability of FTY720a drug that blocks exit of lymphocytes from lymph nodes and that has been through phase II clinical trials for treating multiple sclerosis and preventing kidney transplant rejectionto enhance the immunological control of SIV in chronically infected rhesus macaques. We had discovered a completely novel and surprising immunotherapy that leads to complete clearance of an otherwise chronic infection of LCMV in the mouse. For a one year pilot project in the SIV/NHP model, we will focus on one of two treatment modes: (1) immediate post-exposure treatment, or (2) treatment of an established of chronic infection. We will choose the latter because of (1) its greater potential impact (in the context of treating HIV), and (2) it is likely to produce data that is more interpretable because we will be able to determine drug-associated changes in viral load relative to known set points (allowing us to use fewer animals). There are three possible results for these experiments: (1) no change in viral load; (2) a drug associated increase in viral load, possibly due to concentrating target cells for infection (CD4+) in lymph nodes; or (3) a drug associated decrease in viral load, as in the LCMV model. If the latter is observed, human clinical trials may be warranted, and it helps that FTY720 has been extensively tested in human clinical trials for treatment of MS and solid organ transplantation.