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02600 AN IN VITRO COMPARISON OF TOPICAL MICROBICIDES FOR THE PREVENTION OF HIV TRANSMISSION Dezzutti, Charlene S* A standardized protocol was used to compare cellular toxicities and anti-HIV activities of candidate microbicides that are formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), CarraguardTM, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5% and 4%), UC781 (0.1% and 1%), and Vena GelTM along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (M?) using an ATP release assay. Additionally, they were tested for their effect on a polarized epithelial monolayer (trans-epithelial resistance; TER). Anti-HIV activity was evaluated by blocking transfer of infectious HIV from epithelial cells to activated PBMCs and blocking PBMC and M? infection. CAP, CarraguardTM, PRO 2000, and UC781 along with their placebos were 20- to 50-fold less toxic than KY-N9 and Vena GelTM. At their nontoxic concentrations, none of the products disrupted the TER. Exposure of the epithelial cell lines to HIV-1Ba-L with all products but KY-N9 and Vena GelTM blocked the transfer of virus to PBMCs. Likewise, all products with the exception of KY-N9 and Vena GelTM inhibited PBMC and M? infection with laboratory-adapted HIV-1(Ba-L and LAI) strains. These results indicate that a comparison of candidate microbicides using this protocol may predict their effect on tissues and anti-HIV activity and may help to determine which product(s) to advance to clinical trials. However, the model still needs to be validated against results from human trials. Dr. Charlene Dezzutti |
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