Effect of the Timing of HIV Infection Treatment on the Reconstitution of the T Cell Receptor Repertoire

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CD4+ T cell depletion is a hallmark of HIV infection and the CD4+ T cell count is useful for staging patients as they progress to AIDS. However, a bulk lymphocyte count does not take into account the diversity of recognition specificities these T cells have. Using a novel quantitative assay of T cell receptor (TCR) genetic diversity, called AmpliCot, we have found that untreated HIV infection is associated with an order of magnitude decrease in blood T cell diversity and that these decreases correlate with CD4+ counts. This pilot study will measure the degree to which T cell diversity can recover after successful antiretroviral treatment. Two hundred patients on HAART with undetectable viral loads for a minimum of one year and CD4+ T cell counts > 400 cells/┬ÁL will have their TCR diversity measured. We hypothesize that HAART may only diversity. Cells from these patients will also be studied with flow cytometry to measure the absolute counts of lymphocyte subsets, and markers of thymic activity and immune activation. We will test whether age, thymic activity, or immune activation determine the extent of TCR repertoire recovery after antiretroviral treatment. Our findings will have implications for the timing of antiretroviral therapy, indications for adjunctive immunotherapy, and predictions for possible consequences of aging in HIV patients. The preliminary data from this pilot study will be used to structure and fund larger studies of the effects of HIV treatment on recovery of the immune repertoire.