This study focuses on post-exposure prophylaxis against a panel of primary HIV-1 isolates, or human cell populations infected with these isolates. Prophylaxis will be investigated with mixtures of human monoclonal and polyclonal antibodies, and CD4IgG, chosen for broad reactivity with multiple HIV strains, and with mixtures of antiviral drugs given independently or together with monoclonal antibodies. Evaluation of antibody mixtures will use, successively, in vitro neutralization assays, a post-exposure infectivity reduction assay (PEIR) carried out with freshly infected PBL, and post exposure prophylaxis in SCID mice reconstituted with human PBL intraperitoneally, or both intraperitoneally and intracutaneously. The latter route of reconstitution permits post-exposure prophylaxis after intracutaneous exposure to mimic accidental """"""""needle stick"""""""" exposures in man. The investigators will study the efficacy of antiviral strategies against both cell-free virus, and HIV infected cell subpopulations, including T cells, macrophages and mature and immature dendritic cells. Post-exposure strategies will be evaluated by the duration after virus exposure that effective protection can be initiated, as well as by cost of therapy.
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