At enrollment, women were assigned in a 1:1 ratio, with the use of fixed-size block randomization, stratified according to site, to receive either a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine or a placebo vaginal ring. Both the dapivirine and placebo rings were manufactured by QPharma under contract with the International Partnership for Microbicides. The dapivirine and placebo rings were indistinguishable, and with the exception of staff members at the central statistical and data management center, investigators and participants were unaware of the randomization assignments until completion of the trial. Women were taught how to insert and remove the vaginal ring and counseled to wear it for the entire month.
Women returned for monthly follow-up visits, which included HIV-1 serologic testing, safety monitoring, and individualized adherence counseling (Table S4 in the Supplementary Appendix). At each visit, a new ring was provided, and the ring that had been used during the previous month was collected. Women were tested monthly for pregnancy, and the study ring was withheld from women who became pregnant; they resumed use of the study ring when no longer pregnant or lactating. All participants received a package of HIV-1 prevention services, including counseling with respect to HIV-1 risk reduction, partner HIV-1 testing, treatment of sexually transmitted infections in participants and partners, and free condoms. (Details regarding the trial design are provided in the Supplementary Appendix.)