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02616 INTRAVAGINAL PSC-RANTES PROTECTS AGAINST VAGINAL TRANSMISSION OF SHIV-162P TO MACAQUE MONKEYS Veazey, Ronald (1) We are currently developing microbicides that may block HIV-1 infection by binding to receptors on susceptible cells and interfere with HIV attachment and/or fusion on mucosal surfaces. Since HIV-1 utilizes one or more chemokine receptors for attachment, we are testing the potential for RANTES analogs to block HIV-1 transmission in rhesus macaques. We have developed an amino-terminus modified RANTES analog called PSC RANTES that is several orders of magnitude more potent than native RANTES for inhibition of HIV replication. To assess its efficacy as a microbicide, Depo-provera treated macaques were intravaginally administered 4 ml of PSC RANTES diluted in saline at concentrations of 1 mM (n=5), 330 uM (n=5), 100 uM (n=5), or 1-10 uM (n=5). Five received saline alone as controls. 15 minutes after dosing, animals were intravaginally exposed to 300 TCID50 of the CCR5-using SHIV162P3. Viral loads in plasma were monitored weekly by RT-PCR. All five macaques treated with the highest dose (1 mM), 4/5 treated with 330 uM dose and 3/5 treated with 100uM dose of PSC RANTES were completely protected against vaginal transmission, as evidenced by undetectable virus in plasma. In contrast, 11/15 macaques in the low-dose groups or control group became infected. These results clearly demonstrate that PSC RANTES provides complete protection against vaginal transmission of a CCR5-utilizing SHIV. Since CCR5- utilizing strains predominate in early mucosal transmission, these findings suggest that this may be an effective strategy for preventing mucosal HIV-1 transmission. Dr. Ronald S. Veazey |
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