This is a Phase 3, multi-center, randomized, placebo-controlled trial to assess the effectiveness of CS gel in preventing male-to-female vaginal transmission of HIV among HIV sero-negative women at high risk for HIV infection. Eligible participants who are HIV negative, at risk for becoming infected, and are willing to use a vaginal microbicide each time they have intercourse throughout 12 months of study participation will be recruited in Port Harcourt and Lagos, Nigeria. The enrollment phase will last until 2,160 women have enrolled. It is anticipated that the enrollment will be completed within 12 months.