QUANTITATIVE IN SITU HYBRIDIZATION--HIV1 RNA CLEARANCE FROM LYMPHOID TISSUE

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Recent advances in therapy for human immunodeficiency virus (HIV) infection have increased our understanding of the clinical course and improved the prognosis of patients infected with HIV. The introduction of protease inhibitors (PI) in combination with nucleoside-analogue reverse transcriptase inhibitors (NRTI) as highly active anti-retroviral therapy (HAART) into clinical care has allowed reduction of HIV therapy. The decay characteristics of HIV in the plasma following HAART have been carefully described. However, upon interruption of therapy or in the event of the emergence of resistant strains of virus, viral load rapidly climbs in the plasma. This suggests that the viral dynamics in the compartments which serve as reservoirs for HIV have different decay characteristics from the same cell types in the peripheral blood. Thus, attention has now turned to compartments other than plasma, especially lymph tissue, to more fully understand the dynamics of viral turnover following a complete response to HAART. The fall in peripheral viral load is almost uniformly accompanied by an increase in CD4+ lymphocytes and a dramatic clinical improvement with a reduced incidence of opportunistic infections and prolonged survival. The mechanisms responisible for this apparent partial immune restitution are poorly understood. The goal of this project is characterize the decay characteristics of HIV within the lymph nodes of patients treated with HAART and its relationship to critical cytokines that are involved in the immunopathogenesis of HIV disease. Excisional lymph node biopsies from patients prior to initiating HAART and on two subsequent time points during the first year of therapy will be obtained and divided into three for immediate preservation. Serum and peripheral blood mononuclear cells (PBMC's) will be preserved at the same time. Multiple approaches of measuring HIV and the cytokines IL-2, IL-4, IL-6, IL-12, IFy, and TNFalpha will be performed as outlined in the methods section. It is hoped that the results obtained from these studies will provide additional insight into the viral dynamics of HIV and potential avenues for augmenting immune restitution as well as to help identify novel therapeutic strategies.