Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

The impact of COVID-19 on sexual behavior, HIV prevention interest, general healthcare access, and other HIV risk factors among trial participants in Malawi, South Africa, Uganda, and Zimbabwe.

Introduction: The COVID-19 pandemic greatly impacted HIV prevention and care globally. The pandemic also had disproportionate impacts on the financial, emotional, and physical wellbeing of women and girls in East and Southern Africa, who were already at increased HIV vulnerability. This study aimed to understand how the COVID-19 pandemic and its response efforts impacted the sexual behavior, HIV prevention interest, general healthcare access, and other HIV risk factors of women and girls in HIV prevention studies. Methods: Using the socio-ecological model (SEM), an explanatory sequential mixed-methods analysis was performed with data from four Microbicide Trial Network (MTN) studies on different populations-adolescent girls and young women (AGYW), pregnant persons, breastfeeding persons, and couples-in Malawi, South Africa, Uganda, and Zimbabwe. Descriptive statistics for outcomes of interest were calculated within each study separately and Chi-squared tests of independence were performed to evaluate associations between study population and outcomes. Excerpts from study qualitative interviews were stratified into code reports which were then summarized into memos with key themes and considerations of the SEM framework to provide context to quantitative findings. Results: Few participants (8/731) had known or suspected COVID-19 infection. Sexual frequency and alcohol use decreased most often among AGYW compared to pregnant or breastfeeding women and couples (p-value < 0.001). The pandemic had little impact on changes in reported HIV prevention interest or access to HIV prevention study products. Healthcare access was impacted for everyone, with couples most likely to report decreases in access (p-value < 0.001). From qualitative interviews, economic instability, adverse mental health, and increased violence due to COVID-19 caused increased strain on other factors related to HIV vulnerability. Conclusions: While interest in HIV prevention did not change and a few HIV risks decreased for most women and girls, other vulnerabilities to HIV increased due to the COVID-19 pandemic, highlighting the importance of continued access to HIV prevention for women and girls. More research is needed to better understand the long-term impact of COVID-19 on HIV prevention and vulnerability in community populations.

Adolescent Girls and Young Women's Experiences with Disclosing Oral PrEP or Dapivirine Vaginal Ring Use: a Multi-Country Qualitative Analysis.

Effective use of oral pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in Eastern and Southern Africa, partly due to stigma and opposition from key influencers. Understanding AGYW's experiences of disclosure of different PrEP modalities to key influencers may inform strategies to motivate uptake and adherence. We analyzed qualitative in-depth interviews and focus group discussions data from 119 participants in the MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) study of oral PrEP and the dapivirine vaginal ring (ring) to explore AGYW's disclosure experiences. We found that AGYW disclosure experiences varied across influencers and product type. The ring was disclosed less often to most influencers, except partners, because it was discreet. Oral PrEP was disclosed more often, because pills were more common and to avoid HIV stigma given that oral PrEP resembled HIV treatment. Ultimately, disclosure typically led most key influencers to support product use through reminders and encouragement. While disclosure yielded positive support from influencers, further community awareness of both PrEP products is essential to reduce potential opposition and perceived stigma.Clinical Trial Number: NCT03593655.

''Ask the way from those who have walked it before"-Grandmothers' roles in health-related decision making and HIV pre-exposure prophylaxis use among pregnant and breastfeeding women in sub-Saharan Africa.

HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers' involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers' health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.

Ring-ing in the Future: Participant and Male Partner Perspectives Regarding Future Use of the Dapivirine Vaginal Ring for HIV Prevention.

Women account for a disproportionate percentage of new HIV infections in sub-Saharan Africa indicating a need for female-initiated HIV prevention options congruent with their lifestyles. The dapivirine vaginal ring for HIV prevention is one such option. We explored the interest of women, who used this ring during the Microbicide Trials Network's ASPIRE and HOPE studies, in using the ring post-licensure and what they perceived as important considerations for future use. We also explored perspectives of HOPE participants' male partners on their involvement in their partners' future ring use. Women appeared keen to use the ring in the future and expressed desires for easy access, support for both ongoing and new users and intense community engagement. In parallel, male partners indicated high levels of interest in supporting their partners' ring use and being involved in ring use decision making. These data offer important insights for ring rollout planning and engagement activities.

Religious leaders' role in pregnant and breastfeeding women's decision making and willingness to use biomedical HIV prevention strategies: a multi-country analysis.

Oral Pre-Exposure Prophylaxis (PrEP) is an established option, and the dapivirine vaginal ring is emerging as a promising strategy for HIV prevention option for women. Because of this, understanding the contextual and cultural factors that will support the increased uptake of these products is crucial. In sub-Saharan Africa, religious leaders may be important stakeholders to involve in product information, education and roll-out. We conducted a sub-analysis of data from 232 participants taking part in the MTN-041/MAMMA study to explore religious leaders' involvement in pregnant and breastfeeding women's health. Study participants viewed biomedicine and spirituality as interlinked and believed that women could seek health-related care from medical experts and turn to faith-based organisations for religious or spiritual needs. Religious leaders were invested in the health of their congregations, endorsed a variety of sexual health strategies, and were eager to learn more about emerging HIV prevention technologies. These data signal the role of religious leaders in supporting their communities, and the importance of involving religious leaders in efforts to roll out new HIV prevention products to facilitate uptake.

The Influence of Perceived Dapivirine Vaginal Ring Effectiveness on Social Disclosure and Ring Adherence.

We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring. These findings suggest the importance of women's internalized ideas about the protective benefits of the DVR in sharing information about the ring and the importance of social support on adherence.

Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial.

We evaluated the acceptability of the 25 mg dapivirine vaginal ring (DVR) as an HIV prevention intervention and its influence on DVR adherence in the MTN-020/ASPIRE phase III trial. Acceptability measures were captured using ACASI at month 3 and end of product use (median 24 months, IQR 15-30). Monthly returned rings were classified as nonadherent if dapivirine release rate was ≤ 0.9 mg/month. Associations between acceptability measures and nonadherence were estimated using Poisson regression models with robust standard errors. At month 3 (N = 2334), 88% reported DVR was comfortable, 80% were unaware of it during daily activities, and 74% never felt it during sex. At exit, 66% were 'very likely' to use DVR in the future. Acceptability was found to differ significantly by country across several measures including wearing the ring during sex, during menses, partner acceptability, impact on sexual pleasure and willingness to use the ring in the future. Risk of nonadherence at month 12 was elevated if DVR was felt during sex at month 3 (aRR 1.67, 95% CI 1.26, 2.23). Risk of nonadherence in the last year of study participation was elevated if, at exit, participants minded wearing during sex (aRR 2.08, 95% CI 1.52, 2.85), during menses (aRR 1.57, 95% CI 1.06, 2.32), reported a problematic change to the vaginal environment (aRR 1.57, 95% CI 1.12, 2.21), and were not "very likely" to use DVR in the future (aRR 1.31, 95% CI 1.02, 1.68). DVR acceptability was overall high yet varied by country. Addressing perceived ring interference with sex, menses, or problematic changes to the vaginal environment in future interventions could help improve adherence, as could embracing sex-positive messaging related to ring use and increased pleasure.Trial Registration ClinicalTrials.gov Identifier: NCT01617096.

Men's Sexual Experiences with the Dapivirine Vaginal Ring in Malawi, South Africa, Uganda and Zimbabwe.

The dapivirine vaginal ring has been well-tolerated and shown to prevent HIV in clinical trials. The ring is female initiated, yet endorsement for use is sought from male partners in many relationships. In clinical studies, participants have expressed worries about men detecting rings during vaginal sex, which introduces concerns about product use disclosure, sexual pleasure, penile harm, inter-partner dynamics, and ring removals. This study reports African men's firsthand sexual experiences with the ring. Qualitative data were captured through 11 focus group discussions and one in-depth interview with 54 male partners of ring-users at six research sites in Malawi, South Africa, Uganda and Zimbabwe. Following a semi-structured guide, and using demonstration rings, vulva and penis models, men were asked to discuss the ring's impact on sex and views on male engagement and ring use. Interviews were facilitated by local male social scientists, audio-recorded, translated into English, and analyzed thematically. 22 (41%) of the male partners reported feeling the ring during sex, often attributed to perceived incorrect insertion. 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.

After their wives have delivered, a lot of men like going out: Perceptions of HIV transmission risk and support for HIV prevention methods during breastfeeding in sub-Saharan Africa.

Female-initiated HIV prevention methods, such as oral pre-exposure prophylaxis (PrEP) and the vaginal ring, may be important risk reduction strategies for breastfeeding women. Given their novelty, information about the sociocultural context and how it influences perceptions of and support for their use during breastfeeding is lacking. To address this gap, we conducted 23 focus group discussions separately with pregnant and breastfeeding women, male partners and grandmothers (N = 196) and 36 in-depth interviews with key informants in Malawi, South Africa, Uganda and Zimbabwe. We analysed the data using a framework analysis method. Overall, breastfeeding was the norm, and participants described the transference of health (e.g., nutrition) and disease (e.g., HIV) to children through breast milk. Participants considered the early breastfeeding period as one of high HIV transmission risk for women. They explained that male partners tend to seek outside sexual partners during this period because women need time to recover from delivery, women focus their attention on the child, and some men are disgusted by breast milk. Participants highlighted concerns about the drugs in oral PrEP transferring to the child through breast milk, but fewer worried about the effects of the vaginal ring because the drug is localized. Women, grandmothers and key informants were supportive of women using these HIV prevention methods during breastfeeding, while male partners had mixed opinions. These findings can be used to tailor messages for promoting the use of PrEP or the vaginal ring during breastfeeding in sub-Saharan Africa.

Narrative sexual histories and perceptions of HIV risk among young women taking PrEP in southern Africa: Findings from a novel participatory method.

Pre-exposure prophylaxis (PrEP) is an important HIV prevention method for adolescent girls and young women (AGYW) in Africa, who are at heightened risk of HIV infection. HIV risk perception is generally a powerful motivator for adoption of HIV prevention behaviours, including PrEP use. While HIV risk perceptions have been evaluated using quantitative measures, these seldom capture how individuals conceptualize and understand risk within local frameworks of meaning. More nuanced understanding may come from qualitative approaches that map these perceptions across the trajectory of sexual histories. Between 2016 and 2018, we implemented a novel participatory method to investigate risk perceptions in interviews with 32 participants in HPTN 082, a study of AGYW's use of PrEP in South Africa and Zimbabwe. Timelines were used to record narrative sexual histories and perceived HIV risk for each relationship. We found that women assessed HIV risk primarily based on their partners' personal qualities and behaviour (especially relating to infidelity); their subjective experience of being treated respectfully; and the practice of perceived 'risk reduction', including younger partners and condoms, even if used inconsistently. A narrative timeline approach grounded in an understanding of young women's sexual histories may increase critical reflection about HIV risks and facilitate risk-reduction counselling with this group.

Qualitative Perceptions of Dapivirine VR Adherence and Drug Level Feedback Following an Open-Label Extension Trial.

BACKGROUND: There continues to be a need for HIV prevention options that women can initiate and use autonomously. The dapivirine vaginal ring (VR) has been shown to have a favorable safety profile and reduce the risk of HIV-1 acquisition. We report on women's experiences with VR adherence during the MTN-025/HIV Open-label Prevention Extension (HOPE) study and responses to Residual Drug Level (RDL) results. SETTING: Ten women at each of the 6 HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were randomly selected (n = 60). METHODS: After confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented. RESULTS: Many women with low RDL release measurements deflected blame onto other factors (the ring, the drug, and faulty testing machines) and distrust of the testing method. The disclosure of RDL results enabled some users to discuss their challenges experienced (fear of partner objections, perceived side effects, and removals during menses). Consistent users reported important motivators (support from others, protection from HIV, and enhanced sexual experiences from the VR). CONCLUSION: The VR provided a sense of security for some women; however, adherence was still challenging for others regardless of it being a female controlled, long-acting HIV prevention technology. Adherence measurements may not be sustainable in the real-world implementation of the VR, although they can be seen as a benefit as they provide a better understanding of actual product use and provide women with a platform to discuss their experiences.

The influence of HIV-related stigma on PrEP disclosure and adherence among adolescent girls and young women in HPTN 082: a qualitative study.

INTRODUCTION: Stigma and disclosure concerns have been key barriers to oral pre-exposure prophylaxis (PrEP) adherence for African adolescent girls and young women (AGYW) in efficacy trials. We aimed to understand the impact of these factors among African AGYW in an open-label PrEP study. METHODS: HPTN 082 was an open-label PrEP study among AGYW (ages 16 to 24) in Harare, Zimbabwe, and Cape Town and Johannesburg, South Africa from 2016 to 2018. Women starting PrEP were randomized to standard adherence support (counselling, two-way SMS, monthly adherence clubs) or standard support plus drug-level feedback. Serial in-depth interviews were conducted among 67 AGYW after 13-week and 26-week study visits to explore experiences of stigma, disclosure and PrEP adherence. We analysed data by coding transcripts and memo-writing and diagramming to summarize themes. RESULTS: AGYW described stigma related to sexual activity (e.g. "people say I'm a prostitute") and being perceived to be living with HIV because of taking antiretrovirals (e.g. "my husband's friends say I'm HIV infected"). Participants who anticipated stigma were reluctant to disclose PrEP use and reported adherence challenges. Disclosure also resulted in stigmatizing experiences. Across all sites, negative descriptions of stigma and disclosure challenges were more common in the first interview. In the second interview, participants often described disclosure as an "empowering" way to combat community-level PrEP stigma; many said that they proactively discussed PrEP in their communities (e.g. became a "community PrEP ambassador"), which improved their ability to take PrEP and encourage others to use PrEP. These empowering disclosure experiences were facilitated by ongoing HPTN 082 study activities (e.g. counselling sessions, adherence clubs) in which they could discuss PrEP-related stigma, disclosure and PrEP adherence issues. CONCLUSIONS: Stigma and disclosure challenges were initial concerns for African AGYW newly initiating PrEP but many were empowered to disclose PrEP use over their first six months of PrEP use, which helped them cope with stigma and feel more able to take PrEP regularly. PrEP programmes can foster disclosure through community and clinic-based discussion, adherence clubs and activities normalizing sexual behaviour and PrEP use, which can reduce stigma and improve PrEP adherence and thus effectiveness.

Negative rumours about a vaginal ring for HIV-1 prevention in sub-Saharan Africa.

Rumours may influence health-related behaviours, including the uptake of and adherence to HIV prevention products. This study assessed the safety and effectiveness of a vaginal ring delivering the antiretroviral dapivirine for HIV prevention in Africa. We explored negative rumours about study participation and the vaginal ring amongst study participants and their communities in Malawi, Uganda, South Africa and Zimbabwe. In total 214 women participated in either single or serial in-depth interviews, or a focus group discussion. Three key findings emerged in the data. Firstly, rumours reflected fears concerning the ring and trial participation. Given the historical-political context of the countries in which the trial was conducted, the ring's investigational nature and its foreign origin, ring use was rumoured to cause negative health outcomes such as cancer and infertility and to be associated with practices such as witchcraft or Satanism. The salience of these rumours varied by country. Secondly, rumours reportedly affected participants' adherence to the ring, and other women's willingness to participate in the study. Finally, participants reported that participant engagement activities helped address rumours, resulting in enhanced trust and rapport between staff and participants.

Reasons for nonadherence to the dapivirine vaginal ring: narrative explanations of objective drug-level results.

OBJECTIVE(S): MTN-020/ASPIRE trial and IPM-027/Ring Study recently proved the dapivirine vaginal ring was safe and effective with consistent use. To optimize the ring's impact, the barriers and facilitators to ring adherence must be understood and addressed. METHODS: Former ASPIRE participants were stratified by age group (18-21; 22-45) and randomly selected at seven sites in Malawi, South Africa, Uganda and Zimbabwe, 12-17 months after trial exit. Using in-depth interviews or focus group discussions, ring use barriers were explored using structured guides and visual tools including individual-level depictions of dapivirine levels detected in plasma and returned rings. 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. CONCLUSION: When presented with objective adherence data, participants provided reasons for intermittent ring use, while simultaneously portraying themselves as consistent ring users. Further research is needed to understand how women could use the ring in a way that fits into the context of their relationships and their lives while still conferring adequate HIV prophylaxis.

Impact of the Dapivirine Vaginal Ring on Sexual Experiences and Intimate Partnerships of Women in an HIV Prevention Clinical Trial: Managing Ring Detection and Hot Sex.

Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants' sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners' interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners' discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves.

Acceptability and use of a dapivirine vaginal ring in a phase III trial.

BACKGROUND: The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. METHOD: Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. RESULTS: We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. CONCLUSION: It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden.