Safety and acceptability of silicone elastomer vaginal rings as potential microbicide delivery method in African women

Background: Vaginal rings are a long-acting dosage form in development for delivery of HIV microbicides. Rings have been marketed in the US and Europe since the mid 1990s for menopausal symptoms and since 2002 for contraception; however, African women, a target population for HIV microbicides, have limited experience with vaginal rings. Methods: A crossover, safety and acceptability study was conducted in healthy, sexually active women at 3 research centers in South Africa and 1 in Tanzania. Women were randomized 1:1 to a placebo vaginal ring for 12 weeks, followed by a 12-week no treatment observation period, or vice versa. Safety was assessed by colposcopy, adverse events, and laboratory assessments. Ring acceptability and adherence were assessed by questionnaires. Results: Of 169 women, 85% completed the study. Ring expulsions and removals were reported by 10% and 11% of participants, respectively. The most common reason for both expulsion and removal was menses related. In most cases (64%), the ring was washed and re-inserted. Eighty-two percent of participants reported no ring removals for the duration of the trial, and 99% of women reported wearing the ring for at least 80% of the time. Male partner interviews indicated that men did not feel the ring during intercourse, that it did not impact their sexual pleasure, and that they did not suffer any side effects from the rings. Ninety-five percent of women found the ring to be very comfortable. Vaginal candidiasis was the most common adverse event, occurring in 11% of women during each period. Vaginal discharge (2%), vaginal odor (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the ring, and occurred with similar frequency in the observation period. One SAE of appendicitis was assessed as probably not related to the ring. Thirty-four percent of participants had STIs at screening, and 12% had STIs at the crossover and final study visits. Three participants (2%) tested HIV positive during the study, two at the crossover visit and one at the final visit. All questionnaire responders were willing to use the vaginal ring if shown to be effective for HIV prevention. Conclusions: The vaginal ring was safe and well tolerated for 12 weeks in African women. Participant removal of the ring for menses and cleaning indicates a need for enhanced adherence counseling. All study participants found the ring acceptable and would use it if shown to prevent HIV infection.