MTN-032

Primary Objectives

• To explore socio-contextual and trial specific issues which affected participants’ adherence to the dapivirine vaginal ring (VR)
• To explore male partner attitudes towards and experiences with the dapivirine VR, and their perspective of their female partner’s attitudes and experiences

Study Summary
MTN-032 was an exploratory study primarily designed to identify factors that may have affected participant adherence to study product in MTN-020 (ASPIRE) and MTN-025 (HOPE). The study also elicited perceptions about various participant engagement and adherence promotion interventions implemented in ASPIRE and explored the potential use of incentives to promote adherence to VR use as well as suitable approaches to market the study product.

In the first phase of MTN-032, 187 ASPIRE participants with varying levels of adherence to the dapivirine VR were enrolled. Based upon participants’ plasma dapivirine levels and residual drug levels from returned VRs, participants were pre-selected and approached for study participation. Enrolled participants were categorized into groups of low or high adherence. After being presented their ASPIRE ring adherence results (plasma dapivirine levels and residual drug level results), participants were asked to complete a single in-depth interview (IDI) or a focus group discussion (FGD) (e.g., with other participants with similar adherence levels) where factors influencing adherence, as well as strategies used to overcome adherence challenges, were explored. Intermittent and strategic use around study visits were also discussed.

In the second phase of MTN-032, 115 participants who took part in HOPE, an open-label extension trial to ASPIRE, were enrolled. This phase explored both female participant and male partner attitudes toward the ring. Specifically, female IDIs examined the effect of known efficacy level on adherence. Other aspects, such as their motivation to enroll and continue study participation, the effect of any knowledge of the ring’s efficacy on adherence, and VR uptake, marketing and roll-out were also explored. The attitudes of male partners were explored through focus group discussions, specifically their experiences of and support for partner ring use, their understanding of ASPIRE trial and the impact on support for ring use and their perception of sexual health risk and support for partner’s use of HIV prevention products.

MTN-032 completed follow-up on December 19, 2018. Phase 1 results were presented at the International AIDS Society (IAS), HIV Pathogenesis, Treatment & Prevention meeting held on July 23-26, 2017, in Paris, France. The primary manuscript was published in AIDS on July 17, 2018. Phase 2 results from female participants 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 on female participants was published in Journal of Acquired Immune Deficiency Syndromes on April 1, 2021. Phase 2 results from male partner participants were presented at the IAS Conference held virtually on July 6-10, 2020. The primary manuscript on male partner was published in AIDS and Behavior on January 2, 2021. A total of seven papers have been published from this study.

Phase 1 Primary Results
A total of 187 were enrolled; 37% were 18-21 years when they began ASPIRE. Most (75%) had drug-level results, suggesting inconsistent ring use throughout ASPIRE. Participants viewed themselves as adherent, while simultaneously describing regular instances and reasons for ring removal (e.g., for sex or menses). Less adherent women reported fears that partners would oppose the ring or feel it during sex. High adherers expressed altruistic motivations for ring use. Women of all ages attributed young women's nonadherence to their tendency to be less 'serious' about the future, HIV prevention and the study; motivated predominantly by benefits; more fearful of fertility-related consequences; and to having less relationship control.

Phase 2 Primary Results
A total of 58 female and 55 male participants were enrolled. Analysis of data from the female participants showed various reasons for non-use of the vaginal ring, including menses, vaginal discomfort, and partner objection. However, numerous reasons for using the ring were also mentioned, the most common being protection from HIV. Female participants also reported using the ring more consistently than was indicated by their residual drug scores. Participant barriers and motivators for using the ring as reported during the study shed light on how the ring is incorporated into women’s lives and provide insight to help facilitate real-world introduction of the dapivirine ring.

Analysis of data from the male partners showed that many men described the ring as "scratching" the tip of their penises, and sensations of "prodding" something that "blocked" the vagina and prohibited "full entry". In most cases, feelings dissipated with time or when sexual fluids increased. Less common descriptions included perceiving the vaginal texture, wetness, and size as different, which increased pleasure for some, and decreased for others. Over half (59%) never noticed the ring; some attempting and failing to feel it during intercourse. A majority of men reported that the ring did not lead to changes in sexual positions, feelings, frequency, or experience of sex, although some were initially afraid that the ring was a "magic snake" or "potion". Male partners expressed strong opinions that ring use was a shared prevention responsibility that men should be engaged in, especially for maintaining trust and open communication in relationships. The ring was noticed by many male partners, particularly during women's initial stages of ring use, although this led to few sexual problems or changes. Nevertheless, results suggest that risk of ring discovery should be discussed with women to mitigate any potential negative reactions or social harm. Strategies to increase male partner engagement will enhance support of this prevention method for women.