This is a double-blinded, randomized, safety, acceptability, pharmacokinetic, and ex vivo efficacy study of three rectally-applied tenofovir-based microbicide formulations. Approximately 18 total evaluable HIV-negative men and women (~9 per site) will be enrolled across two study sites: University of California at Los Angeles (UCLA) and Magee-Womens Research Institute (MWRI) at University of Pittsburgh.