Each participant will experience seven rectal exposures to the rectal-specific formulation (RF) and seven rectal exposures to the reduced glycerin vaginal formulation (RGVF) of tenofovir 1% gel, but only one exposure to the vaginal formulation (VF), which will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance out the VF study stage. Participant accrual will take approximately 6 months and each participant will be on study for approximately 3 months. The total duration of the study will be approximately 1 year.