EVALUATION OF FUSION INHIBITORS AS MICROBICIDES FOR SHIV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Vaginal ring devices are being developed to provide sustained release of HIV microbicides. To date, only limited pharmacokinetic data is available from animal or human studies. Here we are determining the pharmacokinetic (PK) and pharmakodynamics (PD) or microbicide candidates CMPD167 and maraviroc in vaginal fluids and plasma after delivery in various formulations including saline, hydroxyethylcellulose gel, silicone elastomer gel, and solid vaginal ring formulations. We have found that gels deliver a very high and rapid dose to the vagina, which is partly absorbed in the systemic circulation (plasma). The delivery by gels is also more sustained compared to PBS, but inferior to ring formulations after a few hours. Rings deliver a semi-constant rate of microbicide delivery over time (28 days is what we have tested to date) and we have now switched to vaginal rings for most of our microbicide testing. Currently we have a series of ongoing studies testing the ability of microbicides formulated in rings (CMPD167 and maraviroc) to prevent SHIV vaginal transmission in challenge experiments.