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02639_2 THE EVALUATION OF MICROBICIDES TO PREVENT HIV-1 INFECTION OF HUMAN COLO-RECTAL TISSUE EXPLANTS Watts, Patricia Background: With 42 million people now living with HIV-1/AIDS, suitable strategies for the prevention of HIV transmission need to be developed. The potential of microbicides to reduce transmission across mucosal surfaces has been clearly identified. The development of microbicides for vaginal application is now well advanced, with some potential agents already having entered clinical trials. However, the prevalence of anal intercourse amongst heterosexual couples highlights the urgent need to assess the effect of these microbicides on HIV infection of rectal tissue. Assessment of their efficacy to prevent transmission across the colorectal mucosa needs to be completed within a suitable tissue model to ensure their efficacy. We present a model of colorectal explant culture to evaluate the efficacy of potential microbicides. Methods: Tissue explants, exposed to HIV in the presence of candidate microbicides were assessed for viral replication by the presence of p24 in culture supernatants, and proviral DNA within Proteinase-K digested tissue. Results: Experiments using microbicidal compounds demonstrated that such compounds have the ability to block HIV-1 infection of colorectal tissue. Inhibition of HIV-1 BaL infection was observed with both polyanionic compounds such as PRO 2000, dextrin sulphate, cyanovirin-N, and cellulose acetate phthalate, and reverse transcriptase inhibitors such as PMPA and UC781. Conclusions: The colorectal explant culture model can be used for the pre-clinical assessment of potential rectal microbicides to prevent HIV-1 infection. Miss Patricia Watts |
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