HPTN 059 is a multi-center phase II study is to determine the safety of tenofovir 1% gel as a vaginal microbicide over 24 weeks, and to gain additional information regarding product''s acceptability. This study will be a four arm, randomized controlled trial, comparing two frequencies of use (daily and coitally dependent), and corresponding placebo gel arms. Half of the participants across cohorts will take part in the "standard safety" study and have pelvic exams without colposcopy. The second half of the participants will take part in an "expanded safety study" and will have pelvic exams with colposcopy and specimen collection for cytokine testing. All participants will be counseled to use, and will be provided with, male latex condoms. Participants will be counseled to use the study products daily or with each act of vaginal intercourse.