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Session 82 Poster Presentations
Microbicides
Session Day and Time: Tuesday 1:30 - 3:30 pm
Room: Hall A


677a
hu-SCID Mice Vaginal/Rectal Model for Safety and Efficacy Testing of Topical Microbicides: Inhibition of HIV-1 Transmission by Gel Containing an NNRTI - TMC120.
Simonetta Di Fabio*1, Giacomo Giannini1, Jens Van Roey2, A. Binelli1, M. Spada1, Guy Van den Mooter3, Caterina Lapenta1, P. Sestili1, M.P. Pirillo1, F. Belardelli1, E. Proietti1, Marie-Pierre de Bethune2, Stefano Vella1
1Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy; 2Tibotec-Virco NV, Mechelen, Belgium; and 3Laboratorium voor Farmacotechnologie en Biofarmacie, University of Leuven, Belgium

Anti-HIV topical microbicides able to prevent virus transmission between sexual partners should be safe and effective when used vaginally and/or rectally. Since few animal model are available suitable for both mechanisms of sexual transmission of HIV-1, our laboratory has developed, in addition to the previous vaginal model, a hu-SCID mouse rectal model. We report the successful: (i) development of a hu-SCID mouse rectal model of sexual transmission of cell-associated and free HIV-1virus; (ii) prevention of a vaginal transmission of HIV through the application of a gel formulation containing a non-nucleoside reverse transcriptase inhibitor NNRTI-TMC120. Gels made up of carbopol 940 or hydroxyethyl cellulose (HEC), two water soluble polymers, were prepared containing TMC-120 in different concentrations (0.225mM; 0.0225mM or 0.00225mM). Animals received a single intravaginal application of 25 ml of gel containing TMC-120, 15-20 minutes prior to a non invasive vaginal challenge with 2x106 human peripheral blood lymphocytes PBL (hu-PBL) previously infected in vitro with non-syncitium (NSI) strains of HIV-1 (SF162 and 1/BX08). Cell to cell transmission was assessed by p24 production and by quantitative PCR. Systemic infection was successfully inhibited by TMC-120 containing gel in this model as shown by p24, and PCR results. This recently developed rectal model is currently being used for evaluation of rectally applied topical microbicides.