al dapivirine vaginal rings have been developed using different polymers and manufacturing processes.24 29 The initial dapivirine vaginal rings evaluated clinically contained either 25 mg or 200 mg dapivirine in a tin catalysed BIIB021 CNF2024 silicone reservoir ring, containing a central drug filled core enclosed by an non medicated outer ring.27,30 The vaginal rings were found to be safe and well tolerated, successfully delivering the drug in vaginal fluids and tissue in the vagina and cervix, with low systemic absorption. Concentrations of dapivirine throughout the lower genital tract were greater than three logs higher than the in vitro EC 50. A subsequent study compared a tin catalysed dapivirine reservoir vaginal ring to a matrix type configuration, in which the drug is uniformly distributed throughout the silicone.
29,30 Similar to the reservoir ring, the dapivirine matrix vaginal ring had a good safety profile with low systemic exposure and high concentrations of drug throughout the lower genital tract. A platinum catalysed silicone ring, designed to improve stability, has been evaluated in phase I and phase II clinical studies WZ3146 EGFR inhibitor involving more than 300 women, and has confirmed the good safety and a pharmacokinetic profiles of earlier prototypes. The ability of vaginal rings to release the drug over prolonged periods of time allows for a monthly dosage form that may contribute to greater consistency in product use.31 Studies assessing the acceptability of vaginal rings for contraception showed that they can be successfully used by women.
Favourable characteristics most often reported by women in these studies included individual control over ring insertion and removal, not needing to remember to take a daily pill, and comfort and ease of use.20,32 35 Compared with other GSK1059615 contraceptive dosage forms, women reported convenience, frequency of use and lower risk of unintentional non use as being the primary reasons for choosing the vaginal ring.36 38 A pattern of more consistent use is supported by the results from a cross sectional multicentre study of 26,250 typical users of a combined hormonal contraceptive showing that emergency contraceptionwas requested by 14% of pill users, 11% of patch users and 6.3% of ring users.39 More recently, several studies have been conducted in an effort to determine the acceptability of vaginal rings for HIV prevention in populations at high risk of HIV infection, specifically in sub Saharan Africa.
In a study of attitudes towards hypothetical use of vaginal rings among female sex workers and their clients in Kenya, perceived benefits of vaginal ring use included a lack of required preparation and inhibition of sexual spontaneity, and compatibility with dry sex preferences. Potential concerns included comfort, detection by male partner, and vaginal hygiene during prolonged use.40 Acceptability during actual use of a placebo vaginal ring in a clinical safety and acceptability study in South Africa and Tanzania was high, with most women reporting that the ring was comfortable, easy to insert and remove, and could be used without male partner knowledge. A minority of women were concerned about the ring getting lost within the body or being expelled. Given its ease of use, stability for more than 2 years in zone 4 conditions,