One of the most well described consequences of HIV-1 infection is progressive loss of CD4 lymphocytes. This progressive cell loss may be a result of increased peripheral destruction of CD4 lymphocytes, decreased production of T-cell precursors and/or redistribution of CD4 lymphocytes from peripheral blood to tissues. Multiple studies of HIV infected patients treated with potent antiretroviral therapy have demonstrated increases in CD4 lymphocytes in response to these therapies. It is unclear if these increases result from decreased destruction, increased new synthesis of T-lymphocytes in the thymus or peripheral tissues or redistribution of sequestered lymphocytes from lymphoid tissues. Recently a new method for measuring in vivo cell proliferation has been developed by Dr. D. Macallan and colleagues. This method uses a non-radioactive isotope to label the deoxyribose moiety of deoxyadenosine which is subsequently isolated from cellular DNA and quantified by mass spectrometry. This labeling technique combined with fluorescence activated cell sorting (FACS) will allow for measurement of newly synthesized naive and memory CD4/CD8 cells. We propose to use this technique on a subset of HIV infected patients who are currently on potent antiretroviral therapy or who will be initiating potent anti-retroviral therapy to contribute to our understanding of immune reconstitution following HAART.
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