This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Advancing our studies on PC-815 (Carraguard plus 50-micromolar of MIV-150) under protocol 3219, we are exploring the microbicide activity of PC-1005 (Carraguard plus 50-micromolar of MIV-150 and 0.3% zinc). Animals received daily applications of gel for 2 weeks and were then vaginally challenged with SHIV RT 4-8h after the last gel. Initially, we observed 100% protection when the animals were challenged 4h after the last gel and subsequent studies have confirmed that this protective capacity persisted for up to 8h (0/7 infected in each group compared to 9/10 in the placebo group). This demonstrates that PC-1005 is more effective at preventing infection that PC-815 (2/6 infected) or Carraguard (4/6 infected). The next studies will test whether PC-1005 remains effective for up to 24h post the last gel application. We also plan to include the additional control of PC-707 (Carraguard plus 0.3% zinc) to determine if the increased activity of PC-1005 is due to the combination of MIV-150 and zinc or zinc alone. The animals will get challenged in March and these initial studies on PC-1005 are expected to be completed by the end of the year. PK studies are planned to be run in parallel to these final efficacy studies.