MTN-034

Primary Objectives

• To compare the safety profiles of FTC/TDF oral tablet administered daily and dapivirine (25 mg) vaginal matrix ring inserted once every 4 weeks during the first 24 weeks of use of each study product in an adolescent and young adult female population
• To compare adherence to the FTC/TDF oral tablet administered daily and to the dapivirine (25 mg) vaginal matrix ring inserted once every 4 weeks during the first 24 weeks of use of each study product in an adolescent and young adult female population

Study Summary
MTN-034 was a Phase 2a, multi-site, randomized, open-label, crossover study to assess safety and adherence of a dapivirine vaginal ring and oral emtricitabine/tenofovir (FTC/TDF) tablets in HIV-uninfected adolescent females between the ages of 16 - 21 years old (inclusive). The primary objectives of MTN-034 were to collect safety and adherence data for these two study products in an adolescent population and to provide important information regarding individual preference for the products. This trial enrolled 247 healthy, HIV-uninfected, adolescent females. Participants were randomized (1:1) to one of two study product application sequences: (a) daily FTC/TDF oral tablets for 24 weeks, followed by use of the dapivirine VR inserted monthly for 24 weeks; or (b) monthly dapivirine VR for 24 weeks, followed by daily FTC/TDF oral tablets for 24 weeks. After completing the randomized sequence of two study product use periods, participants then selected one of the study products (or neither) to use in the third and final 24 weeks of the trial. In total, participants were followed up for approximately one and a half years. Participants could choose either or neither study product at any time during the third product use period.

MTN-034 completed study follow-up on September 9, 2021. The interim primary results were presented at the 11^th IAS Conference on HIV Science held virtually on July 18-21, 2021. The primary results from the choice period were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) held virtually on February 12-16, 2022. A total of 13 abstracts and one paper have been published from this study. Primary and secondary manuscripts are in development.

Interim Primary Results
247 AGYW were enrolled with an average age of 18. Twenty-six months into the study, retention to study visits is 94.4%. Approximately 35% of participants had at least 1 sexually transmitted infection at baseline (chlamydia: 28.7% [71/247]; gonorrhea 8.5% [21/247]). Most participants had at least moderate adherence to ring (77.8% [1064/1368]) and oral PrEP (58.6% [768/1310]). High adherence was observed in 50.2% of ring and 22.4% of oral PrEP users (687/1368 and 294/1310 of timepoints). AEs of grade 2 were experienced by 78% (187/241) of ring users and 77% (188/245) of oral PrEP users. Acceptability varied, with 88.5% (193/218) liking ring and 63.9% (140/219) liking oral PrEP. One HIV acquisition and 4 incident pregnancies were reported.

Choice Period Primary Results
Participants’ average age was 18 years, and of 227 (92%) who continued in the choice period, 152 (67%) chose the ring, 71 (31%) oral PrEP, and 4 (2%) neither. Randomization sequence in the crossover period did not influence product choice. Residual DPV levels in used rings and TFV-DP levels in DBS showed participants had some to high use of the ring and moderate to high adherence to oral PrEP with <5% of visits with no adherence. High adherence to oral PrEP in the crossover period was strongly associated with choice of oral PrEP (p<0.001); an association was not observed for rings (p=0.85).