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02646_2 HU-SCID MOUSE MODEL FOR RECTAL TRANSMISSION OF HIV: TESTING PRO 2000/5 GEL. Di Fabio Simonetta §*, Topical microbicides for the prevention of HIV-1 transmission between sexual partners should ideally be safe and effective when used both vaginally and rectally. Few animal models are suitable for evaluating both mechanisms of sexual transmission. Our study focuses on the use of a hu-SCID mouse model of cell-associated HIV transmission at the rectal level. This recently developed rectal model is currently being used for evaluation of rectally applied topical gel containing PRO 2000/5 at two different concentrations (0.5%, and 4%) vs a matched placebo gel. Animals received a single intra-rectal application of 50 ?l of PRO 2000/5 or placebo gel, 15-20 minutes prior to a non-invasive rectal challenge with cell-associated dual-tropic laboratory-derived R5X4 strain of HIV-1 (1/BX08). Cell to cell transmission was assessed by p24 determination and by quantitative PCR. Systemic infection was inhibited by PRO 2000/5 gel in this model: 4 out of 5 animals (80%) receiving 4% PRO 2000/5 gel resulted negative for infection as shown by p24 and PCR results, and 4 out of 5 animals (80%) receiving 0.5% PRO 2000/5 gel resulted negative as shown by p24 results. All 5 animals receiving the placebo gel became infected. We are currently confirming these preliminary results and investigating the effect of PRO 2000/5 gel in preventing the rectal transmission of cell-free virus. MD, PhD, Simonetta Di Fabio |
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