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02560 SYNERGY BETWEEN POTENTIAL HIV MICROBICIDAL AGENTS Fowler, Katherine* Polyanionic microbicides such as Dextrin-2-sulphate (D2S) and PRO2000 are currently in Phase II trials. However, it is unlikely that microbicides will be used alone to prevent HIV infection due to the problem of resistance seen in monotherapy. The aim of this work was to study the anti-HIV-1 interactions of D2S and PRO2000 with other known antiretroviral agents in vitro. Combinations of D2S and PRO2000 with the neutralising monoclonal antibody IgG1B12, the peptide-based fusion inhibitor DP178, the CCR5 antagonist TAK779 and the bacterial anti-HIV-1 agent Cyanovirin-N were assessed for their ability to act in synergy against HIV-1JR-FL, HIV-1HxB2 and HIV-1W61D pseudoviruses. These pseudoviruses have the luciferase gene inserted into nef allowing quantitative analysis of viral infection 3-5 days post infection, and are only capable of a single round of replication. The data were analysed for synergy using Calcusyn software. Results using HIV-1JR-FL indicate that PRO2000 acts synergistically with IGG1B12 and PRO2000 acts in synergy with DP178 at high concentrations of both drugs. These findings suggest that it may be beneficial to use PRO2000 in combination with other known antiretroviral agents. By contrast, combinations of D2S with IgG1B12 and DP178 are antagonistic for inhibition of HIV-1JR-FL infectivity. These data suggest that polyanionic microbicides can exhibit synergistic anti-HIV-1 activity in combination with other types of inhibitor, but that combinations must be studied on a case by case basis. Miss Katherine Fowler |
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