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02414 SAFETY AND EFFICACY OF CELLULOSE ACETATE PHTHALATE (CAP) AGAINST VAGINAL TRANSMISSION OF SIMIAN/HUMAN IMMUNODEFICIENCY VIRUSES IN RHESUS MACAQUES Boadi, Tina* Cellulose acetate phthalate (CAP), a pharmaceutical excipient designed as a coating material for tablets or granules, has been demonstrated to be effective against herpes simplex virus type 2 (HSV-2) infection in mice, and to protect four of six rhesus monkeys from vaginal challenge with simian immunodeficiency virus SIVmac251. Formulated CAP applied vaginally to rhesus macaques was not irritating as determined by colposcopy. Serum chemistries, vaginal biopsies, bacterial cultures and vaginal pH were all within normal limits. No obvious changes in peripheral CD4:CD8 ratios or levels of inflammatory cytokines/chemokines in plasma and vaginal fluids were detected. Thus, CAP appears to be safe in vivo. Magnetic resonance imaging (MRI) revealed that CAP was evenly distributed after application and 20 min thereafter, but was found absent 24h after application. To assess whether CAP confers protection against primary viral strains that are transmitted in humans, infections with simian/human immunodeficiency viruses (SHIVs) expressing the envelopes of X4 and R5 HIV-1 strains (SHIVSF33A and SHIVSF162P3, respectively) were performed. Replication of SHIVSF33A and SHIVSF162P3 in vitro can be efficiently blocked by CAP, with ID50 concentrations of 180 and 25 mg/ml respectively. Preliminary findings in rhesus macaques challenged with a mixture of X4-SHIVSF33A and R5-SHIVSF162P3 suggest that CAP is efficacious against both X4 and R5 SHIV viruses in vivo, and should therefore be considered as a viable topical microbicide candidate in the prevention of HIV-1 infection. Research Assistant, Tina Boadi |
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