Breaking Down Relationship Barriers to Increase PrEP Uptake and Adherence among Adolescent Girls and Young Women in Kenya: Safety and Preliminary Effectiveness Results from a Pilot Cluster-randomized Trial

"...Tu'Washindi increased PrEP uptake and adherence..."

In Kenya, adolescent girls and young women (AGYW; ages 15-24) who live in a context of heightened gender inequality and intimate partner violence (IPV) risk are uniquely vulnerable to HIV acquisition and face exacerbated barriers to oral pre-exposure prophylaxis (PrEP) use. In light of these challenges, researchers partnered with AGYW in Siaya County, Kenya, to develop and pilot test Tu'Washindi na PrEP (We're Winners with PrEP), a multilevel, community-based intervention that aims to increase PrEP use by addressing relationship- and violence-related challenges. This paper presents results on intervention safety (i.e., IPV and social harms) and effectiveness on PrEP uptake, continuation, and adherence.

All study activities were nested in the DREAMS programme, which is a public-private partnership aiming to reduce HIV incidence among AGYW through activities including: school- and community-based HIV and IPV prevention; referrals for post-violence care; re-enrolment of girls in schools; provision of HIV counselling and testing, condoms and contraception, and PrEP; and social asset building through "safe spaces".

The researchers used participatory methods, engaging local AGYW and DREAMS providers to co-design an intervention that could be easily integrated into ongoing DREAMS activities and to deliver supplemental, targeted content. The intervention included 3 components delivered over 6 months to these groups:

• AGYW - via an 8-session empowerment-based support club. The intervention primarily sought to address partner-related barriers to PrEP use, but support club sessions also aimed to increase knowledge, skills, self-efficacy, and social support around PrEP use for AGYW participants. Sessions occurred biweekly for the first 2 months and monthly thereafter, and they were facilitated by a safe space mentor or by a participant with mentor support. DREAMS clinicians and counsellors led specific activities.
• Male partners of AGYW - via community sensitisation events that were led by male "change agents" from the SASA! programme (delivered though DREAMS), with support from DREAMS clinicians. Events were scheduled weekly over the first 3 months in places where AGYW's male partners are known to gather (e.g.m boda boda [motorbike taxi] drivers' meetings, chief's meetings [barazas]).
• AGYW and their male partners - via couples' PrEP education events called "buddy days". These events were held at each intervention safe space in month 3 of the intervention period, co-facilitated by the change agent and clinician. To destigmatise participation, buddy days were open to all community members and offered routine health services.

Tu'Washindi na PrEP was piloted in a cluster-randomised controlled trial (RCT) conducted at six DREAMS sites from April to December 2019. Participants were 103 AGYW aged 17-24, HIV negative, and either eligible for, or already taking, PrEP. Over 6 months of follow-up, the researchers assessed IPV (months 3 and 6) and PrEP uptake and continuation (month 6) through interviewer-administered questionnaires; PrEP adherence was assessed with Wisepill electronic monitoring devices. Adherence was defined as the number of days with a Wisepill opening during the self-reported period of PrEP use.

One-third of participants were currently taking PrEP, and 45% reported IPV in the past 3 months. Retention was 97% at month 6. Compared to the control arm, intervention arm participants were more likely to initiate PrEP, if not already using it at enrolment (52% vs. 24%, adjusted risk ratio (aRR) 2.28, 95% confidence interval (CI) 1.19-4.38, p = 0.01), and those taking PrEP had more days with Wisepill device openings (25% of days vs. 13%, aRR 1.94, 95% CI 1.16-3.25, p = 0.01). Twenty percent of participants reported IPV during follow-up. There were trends towards fewer IPV events (aIRR 0.66, 95% CI 0.27-1.62, p = 0.37) and fewer events resulting in injury (aIRR 0.21, 95% CI 0.04-1.02, p = 0.05) in the intervention versus control arm.

Tu'Washindi's promising results may stem from three design elements:

1. The intervention was designed "from the ground up", based on formative research to understand the specific needs of AGYW in this context, and with meaningful involvement of AGYW and their service providers through a design workshop that informed selection and development of key components. The originally planned intervention was largely redesigned based on these activities.
2. It worked at the community, partner, and individual levels to simultaneously address multiple factors influencing PrEP use and vulnerability and to build women's agency by helping them identify a range of actions they can take to achieve their health and relationship goals, even in the context of oppressive gender norms. Most existing PrEP support interventions have focused on individual-level barriers and facilitators.
3. It used a gender-synchronous approach, including both separate and joint activities for men and women, incorporating findings from prior studies that working only with women can lead to male resistance and that providing opportunities for men to engage in dialogue on their own and jointly with women and girls can support behaviour change.

In short, the results indicate that intervention participants had approximately two-fold higher PrEP uptake and adherence than control arm participants, with no evidence of increased IPV or social harms. There were also significantly lower rates of IPV in the intervention arm among participants with a prior history of IPV, suggesting that the intervention might also be an effective IPV reduction strategy. However, PrEP adherence remained low among intervention arm participants, suggesting the need to reduce barriers not addressed by Tu'Washindi, such as stigma, risk perception, side effects, and pill fatigue. Promising approaches could include community-wide education to reduce stigma, decision support tools, and the provision of new PrEP delivery modalities, such as the ring or injectable PrEP, which may reduce user burden. Future efforts could include adapting Tu'Washindi or delivering it in conjunction with other interventions to incorporate these strategies.

In conclusion, this RCT "underscores the importance of designing interventions in collaboration with local stakeholders; engaging AGYW and their male partners individually and as couples; and working across socio-ecological levels to address partner and relationship factors contributing to HIV and IPV. Given the important role of male partners in supporting or obstructing PrEP use, and the consequences of PrEP use for relationship health, future research should develop and test additional approaches to build male partner support and ensure that these approaches can be feasibly scaled up and delivered alongside ongoing programmatic efforts addressing other barriers to PrEP use and HIV prevention."