MTN-005

Primary Objectives

• Evaluate adherence to the study intravaginal ring in HIV-uninfected women over 12 weeks of use
• Evaluate the safety of the study intravaginal ring in HIV-uninfected women over 12 weeks of use

Study Summary
MTN-005 was a multi-site, randomized, open-label, two-arm, controlled trial of a non-medicated intravaginal ring.  A vaginal ring delivery system for microbicides has the potential to minimize adherence problems found with the use of daily or coitally-dependent dosing regimens. This study evaluated the safety and adherence to intravaginal ring use in women in the U.S. and India. The study enrolled 195 healthy 18 to 45 years old women who were HIV-uninfected, sexually-active, and using adequate contraception. Participants at two sites in the USA and a single site in India were randomized to one of two study arms:  intravaginal ring use or no ring. MTN-005 also examined the impact of 12 weeks of intravaginal ring use on vaginal flora. Studies have shown that the presence of H2O2-producing vaginal lactobacilli offers a protective effect against sexually transmitted infections. There were no previously published data on the impact of intravaginal ring use on quantitative measures of vaginal flora.

The study completed follow-up on September 20, 2012. A primary manuscript was drafted but not published as study data quality was affected by product holds and enrollment discontinuation due to the presence of air pockets in the rings attributed to the manufacturing process.

Primary Results
A total of 195 healthy, sexually active women were enrolled across one site in India and two in the US. 369 AEs occurred and 153 (78%) participants experienced at least one AE. In the IVR arm, 271 AEs were reported with 173 (64%) designated as unrelated to the study IVR. Each of the 98 AEs in the no IVR arm was considered by the investigators to be unrelated. The four reported Grade 3 AEs were designated as unrelated. There were no Grade 3 genitourinary AEs and no Grade 4 or 5 AEs in either arm. No statistically significant differences were detected in the number of participants with at least one Grade 2 genitourinary AE between the two arms (p=0.33). Fifty-two (27%) of 195 participants enrolled in the study experienced at least one product hold with the majority (n=49) occurring at the India site, mostly due to the finding of dark spots on a portion of the IVR. Among 130 participants evaluable in the IVR arm, 75 (58%) reported complete adherence with IVR insertion, with the rate of adherence similar between the U.S. sites (60%) and the India site (56%). In conclusion, the non-medicated silicone elastomer IVR used in this study was safe and acceptable and over half of women reported complete adherence over the course of the study. These findings suggested the silicone elastomer ring is a suitable vehicle for drug delivery in the vagina, including microbicides for HIV prevention.