Keller MJ, Wood L, Billingsley JM, et al. - In sexually active women, researchers investigated the safety and pharmacokinetics of intravaginal rings that release the tenofovir prodrug, tenofovir disoproxil fumarate, over 90 days via a phase 1, single-blind, randomized, placebo-controlled trial. They randomized 17 sexually active women who were HIV negative (3:1) to a tenofovir disoproxil fumarate ring or placebo ring. The participants continuously used the tenofovir disoproxil fumarate intravaginal ring with monthly ring changes for 3 months. In the tenofovir disoproxil fumarate ring group, a complete 3 months of continuous ring use was reported in two participants; because of ulcerations (grade 1) near the ring, eight were asked to discontinue ring use early. Rings were electively removed by study staff on day 20 and day 23 in the remaining two women. In the placebo group, no participants developed ulcers. The eight patients who did vs the four who did not develop ulcers had no differences in cervicovaginal fluid tenofovir concentrations at day 14. The tenofovir disoproxil fumarate ring group but not the placebo group exhibited significantly higher concentrations of multiple inflammatory cytokines and chemokines at days 14 and 28 compared with baseline.