MTN-025

Primary Objectives

• Characterize the safety profile associated with the open-label use of the dapivirine (25 mg) vaginal matrix ring (VR) in women
• Characterize adherence to the open-label use of the dapivirine VR (25 mg) in women

Study Summary
MTN-025, the HIV Open-label Prevention Extension (HOPE) trial, was a multi-site, open-label, Phase 3B trial. Eligible HIV-uninfected former ASPIRE participants were offered a silicone elastomer VR containing 25 mg of dapivirine. Participants could choose not to accept study product at any time and still take part in the study. Study follow-up visits occurred monthly for the first 3 months and quarterly thereafter for 12 months, reflecting a transition to a more real-world type of follow-up (versus a clinical trial approach). The primary objectives of the HOPE study were to assess adherence to and safety of the monthly dapivirine vaginal ring in an open-label setting. Secondary objectives included assessing HIV-1 incidence and HIV-1 antiretroviral resistance. Former ASPIRE participants who chose not to take part in MTN-025 had the option of completing behavioral questionnaires and a subset were selected for qualitative evaluation assessing reasons for non-interest in enrolling (decliner population).

MTN-025/HOPE completed follow-up on October 10, 2018. Results were presented at the 10th International AIDS Society (IAS) Conference on HIV Science held on July 21-24, 2019, in Mexico City, Mexico. The primary manuscript was published in Lancet HIV on February 1, 2021. A total of six papers have been published from this study.

Primary Results
Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR. Among the 35 infections, 7 had NNRTI mutations but none suggest a dapivirine-specific resistance pattern. In summary, high uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa.