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02686 IN VITRO ANTI-HIV-1 ACTIVITY OF MICROBICIDE FORMULATIONS AGAINST NON-SUBTYPE B PRIMARY STRAINS Ramos, A.* In vitro analyses to assess the anti-HIV-1 efficacy of microbicide formulations should include primary virus strains from geographic regions where clinical studies are being proposed. In this study, microbicide formulations of CarraguardTM, cellulose acetate phthalate (CAP), KY plus nonoxynol-9 (KY-N9), PRO 2000 (0.5% and 4%), UC781 (0.1% and 1%), and Vena GelTM were tested against primary HIV-1 strains (subtypes A, C, and CRF01_AE) representing predominant circulating strains in southern Africa and southeast Asia. Microbicides (highest non-toxic concentrations) were added to peripheral blood mononuclear cells (PBMCs) along with HIV-1 strains. Virus infection of the PBMCs was monitored by HIV-1 p24-antigen in culture supernatants at days 1, 3, and 7 post-challenge, and anti-viral activity of microbicides was measured as log10 reduction of p24 production in the presence of microbicides versus controls (no microbicides). CAP, PRO 2000, and UC781 effectively blocked the infection by the three subtype strains (1.3- 4.5 log10 or 95-100% reduction). KY-N9 completely blocked infection by the subtype A and CRF01_AE strains (2.4-2.8 log10 or 100% reduction) and had a smaller effect on the subtype C strain (0.9 log10 or 88% reduction). CarraguardTM did not block infection by the three subtype strains (-1.3-0.38 log10 or 185-59% reduction). The effect of Vena GelTM on the three subtype strains was variable: a 1.36 log10 (96%) reduction for the subtype C strain but only a 0.2 log10 (38%) and a 0.02 log10 (-4.1%) reduction the subtype A and CRF01_AE strains, respectively. Differences in microbicide efficacies against primary viruses belonging to different subtypes highlight the importance of including primary HIV-1 strains in pre-clinical microbicide testing algorithms. Dr Artur Ramos |
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