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02446 PC-815, A NOVEL COMBINATION MICROBICIDE Romero, Jose Fernandez* The following is a report on PC-815, a novel microbicide that combines the microbicide Carraguard® and the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (Medivir AB). Pre-clinical studies indicate that Carraguard is effective in preventing HIV, SIV, HPV, HSV, and Neisseria gonorrhoea infection in vitro or in animals, and clinical trials show that the formulation is stable, safe, and acceptable in humans. Studies done by Medivir show that MIV-150 is highly efficacious in blocking infection by many HIV strains including strains resistant to other RT inhibitors. Animal studies show that MIV-150 is non-toxic, and clinical trials demonstrate that the compound is well tolerated and not easily systemically absorbed. We present evidence that MIV-150 in Carraguard can neutralize free virus. Strong evidence suggests that PC-815 is more efficacious in blocking infection in lymphoma cells than Carraguard or MIV-150 alone. PC-815 also prevents infection of all clinical isolates of HIV tested in PBMCs. In most cases, PC-815 is an order of magnitude more efficacious than Carraguard. By testing efficacy against HIV in vitro, using HPLC, and measuring the viscosity of the formulation, PC-815 was found to be stable for 3 months at 40OC. PC-815 is, therefore, a promising safe, stable and, efficacious microbicide. Jose Fenandez-Romero |
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