HIV infections among transgender women are 2.2 higher than gay, bisexual, and other men who have sex with men in sub-Saharan Africa due to syndemics consisting of stigma and discrimination that perpetuate violence and victimization, limiting access to HIV prevention and treatment [1-4]. In South Africa, the HIV incidence for transgender women is 31 cases per 100-person years, with studies showing limited pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) access and adherence. Based on other African studies, only an estimated 25% of transgender women are virally suppressed [5-7]. HIV prevalence among transgender women in South Africa mirrors the realities that they share with their peers in other Global South settings, with a 52% mean prevalence documented in 3 South African cities [8]. Transgender women’s health and safety remain compromised in South Africa, inhibiting their ability to engage in HIV services to lower transmission risk and improve their overall wellness, and compounding these health outcomes are poor relationship dynamics.

Being in an unhealthy or imbalanced relationship for transgender women can lower their HIV testing behaviors and increase rates of condomless anal intercourse with partners to create trust and intimacy [9-13]. Fear of partner rejection or loss and intimate partner violence may lead transgender women to limit or halt ART use to conceal their serostatus from partners [14-16]. Further, studies increasingly show that transgender women experience negative outcomes of relationship stigma (when partners fear being romantically associated with someone who is stigmatized), which in turn has hindered their ability to discuss HIV treatment with them [15,17]. Although studies with transgender women in South Africa are limited, in the United States, relationship dynamics for transgender women influence HIV risk, in the same ways they do for cisgender women and sexual minority men [17-21]. Additional factors hindering HIV prevention and treatment discussions that transgender may have with a partner include living with them, drug use, alcohol use, education level, and low self-efficacy to use condoms [18]. In sum, cisheteronormative social structures and power dynamics have been shown to result in increased marginalization, increased susceptibility to intimate partner violence, and increased risk of mental issues among transgender women, all hindering HIV prevention and treatment [22-24].

Further, transgender women are less likely to disclose their HIV status to other transgender women and sexual minority men within their social networks, increasing social isolation [25-27]. Only after being out of care and developing AIDS-related illnesses do transgender women disclose their HIV status to an immediate family member in order to secure support for their treatment, but this disclosure does not extend to partners [25,27]. Given a history of HIV care marginalization and discrimination, transgender women often possess inaccurate knowledge and skills in discussing with partners how PrEP and ART adherence, including “undetectable is untransmissible” (U=U) messaging, can work together to reduce transmission and in turn support relationship health [14-16]. Thus, transgender women have ongoing HIV-related stress without the skills to manage this stress and their disclosure to partners and others for support.

The benefits of social and partner support are significant for transgender women. Studies show that transgender women in committed relationships are less likely to engage in HIV-related high-risk behaviors, with researchers suggesting that relationship stability and emotional support lead to more consistent condom use and improved HIV prevention and treatment overall [28-30]. Specifically, higher relationship satisfaction, trust, and commitment were protective factors against HIV transmission among transgender women [17,31]. Additionally, 1 randomized controlled trial found that a social support group intervention further reinforced relationship-related protective behaviors among transgender women [32]. Therefore, a relationship-focused HIV intervention may support treatment and prevention outcomes for transgender women and their partners while garnering the support of family members earlier in their treatment journey.

To address this gap in interventions for transgender women living with HIV in South Africa, the aim of our study is to tailor our existing intervention, Speaking Out and Allying Relationships (SOAR) intervention, with them and then conduct a 1-arm pilot study to assess intervention feasibility in Eastern Cape, South Africa. Specifically, we will tailor SOAR and assess usability for content understandability and satisfaction (aim 1), and then evaluate its feasibility to include retention and any changes in behavioral and biomedical measures (aim 2). We hypothesize that participants will find SOAR feasible, acceptable, and safe to inform a larger efficacy study.

Our SOAR intervention is based on Healthy Relationships (HR), a 5-session, group-based evidence-based intervention to develop individual HIV disclosure risk assessment and safer sexual behavior skills with partners that have demonstrated efficacy in these outcomes in a range of settings [33,34]. The core elements of SOAR are to: (1) develop coping skills to manage HIV-related stress and sexually risky situations; (2) enhance decision-making skills for HIV disclosure to partners; and (3) establish and maintain safer sex practices with partners. The HR intervention was identified based on our preliminary research with sexual minority men and transgender women in South Africa [35]. Additionally, through this preliminary research, we demonstrated that transgender women are willing to complete HIV-related group work and have an interest in mHealth tools, like videoconference modalities, to learn skills in HIV treatment management and disclosure for support [36,37]. Moreover, harnessing high use rates of smartphones by transgender women for intervention delivery is feasible in South Africa [20,38]. Increased evidence shows that transgender women access web-based social networking sites and use SMS for social networking through mobile and smartphone technologies, creating the potential to tag on ART adherence interventions [39,40]. In our research, we found that HIV-positive sexual minority men and transgender women regularly use videoconferencing to support community networking across rural and urban settings, with 2-hour conversation events focused on HIV, sexuality, and gender [37]. Further, mHealth tools (SMS, chat rooms, and web-based video group interventions) for HIV prevention and treatment in South Africa are part of the national strategic plan [41]. As in the original HR, our SOAR intervention integrates media, scenarios, and roleplays for skill development, and these reflect the experience of South African sexual minority men living with HIV and in relationships. In addition to the standard 5 sessions, we include three 30-minute booster sessions to review action plans over 3 months.

Social cognitive theory serves as the framework for the intervention, which posits that cognition, behavior, and environment interact and influence health outcomes, like HIV risk reduction, disclosure, prevention, and ART adherence. SOAR aims to enhance coping skills for HIV-related stress, self-regulation of disclosure to include risk assessment, treatment, and prevention, and build self-efficacy in healthy behaviors and communication within relationships. Further, the intervention will provide a platform for participants to strengthen coping skills that will support and empower gender affirmation within relationship dynamics that may be experiencing stigma or risk of violence, or desire for improved relationship communication. Within the social cognitive theory model, the intervention will incorporate components such as HIV risk reduction education, treatment education including U=U, HIV prevention strategies like PrEP, and gender affirmation within the context of HIV. Skill-building activities for HIV communication and disclosure risk assessment will be conducted in a confidential group setting. By helping individuals plan for safe sex and consider HIV communication and disclosure to partners, the intervention aims to support ART adherence, empower participants with a sense of agency, and reduce negative feelings associated with their HIV status and internalized HIV stigma.

Our proposed tailoring of SOAR for transgender women is based on high interest to participate among those who attended community outreach activities for recruitment of sexual minority men as part of the original intervention. If this tailoring shows promise of feasibility, then we will conduct a larger randomized controlled trial to assess efficacy and implementation with local agencies that service sexual and gender minority communities in South Africa.

The study will use a 2-fold approach, beginning with intervention tailoring and usability assessment (aim 1) and then a 1-arm pilot study of the intervention (aim 2) to evaluate feasibility. Prior to study initiation, a study coordinator will be hired and trained in study procedures and the SOAR intervention and its delivery approach. The coordinator will be a member of the sexual and gender minority community in Eastern Cape and have a history of HIV program work. Coordinator training will include a review of sexual and gender minority health with a focus on HIV treatment and prevention barriers and facilitators for transgender women, gender-affirming care such as hormone replacement therapy, and relationship dynamics influencing HIV care. Additionally, the coordinator will complete training in good clinical practice and ethics and study procedures including data collection. Finally, the coordinator will be trained in the SOAR intervention which will include both didactic and simulation sessions until competency has been achieved. The study coordinator will conduct all study procedures with mentoring provided by the research team.

In aim 1, we will tailor SOAR by using a human-centered design approach. First, we will assess transgender women’s preferences and confirm their relationship dynamics regarding HIV. Then, we will evaluate the functionality of the intervention in a videoconference format (Zoom, Qumu Corp), and usability by gauging participants’ understanding and satisfaction with the SOAR intervention.

The study will be conducted in Buffalo City Municipality, Eastern Cape, South Africa. In this setting, there is a 46% HIV prevalence among transgender women who live in both urban and rural areas [8]. We will recruit transgender women (N=15) living with HIV and in a relationship for more than a month. Recruitment activities will be conducted by study staff at community events focused on transgender women and sexual and gender minorities. Study staff are members of the sexual and gender minority community and allies, and all completed LGBTQ competency training. Interested participants will be provided study explanation and invited to answer questions in the screening survey. Eligible participants will complete written informed consent in the language of their choosing (eg, isiXhosa, Afrikaans, English). The consent form will outline confidentiality and protections of participant information if they are interested in participating in the study. All participants will receive travel reimbursement and refreshments to complete study procedures.

To assess transgender women’s preferences for the intervention, we will conduct in-depth interviews (IDIs). These interviews will delve into influences on HIV treatment including support and relationship dynamics, and gather feedback regarding various aspects of the intervention, including format and delivery. A semistructured question guide will ask questions in four domains: (1) HIV prevention and treatment knowledge; (2) relationship scenarios involving HIV disclosure and support for role-play development; (3) videoconference delivery preferences; and (4) positive representation of transgender persons in media (web-based, television, and movies) to show during the sessions. Each interview will be 60 minutes long, conducted in the local language (isiXhosa), transcribed verbatim, and translated for analysis. Findings from the analysis will be used to tailor SOAR to the contextual factors influential in HIV treatment and status disclosure for transgender women and to ensure representation of their empowering voices in the roleplays and videos to support skill building.

Usability testing will involve 2 tasks: pretesting and IDIs with participants. We will recruit 7 (50%) racially and relationship-length diverse transgender women participants from step 1 for pretesting. The pretesting phase will span 5 weeks, with 2-hour sessions each week. At week 8, 3 weeks after the last session, a group check-in session will be conducted via Zoom. Participants will receive SMS reminders for each session and the Zoom session link. All sessions will be completed together to foster positive group dynamics and will include a set of group rules for this purpose, and to protect the confidentiality of participants and their contributions during the sessions. The interventionist will monitor participant engagement throughout the pretesting and follow up with any missed sessions. Participants will provide their smartphone numbers for session reminders, self-assessment, action plans, and partner referrals delivered through Research Electronic Data Capture (REDCap; Vanderbilt University). The sessions and group check-in will be video-recorded for analysis, and participants will receive a data plan to facilitate their participation. After the pretesting phase, IDIs will be conducted with racially and relationship-length diverse participants over Zoom. The interviews will cover 6 usability domains for SOAR, including session functionality, timeliness and appropriateness, clarity of content delivery, document clarity and management, incomplete sessions, and technical transitions between sessions. The individual interviews in isiXhosa are expected to last approximately 50 minutes. Audio recordings of the interviews will be transcribed and translated into English for further analysis.

To understand SOAR preferences and usability, interview transcripts will be cleaned and confirmed for accuracy before being uploaded into the qualitative data management program, Dedoose, where data will be coded and categorized [42,43]. First, the research team will separately analyze each transcript using predefined codes and open coding, and then discuss coding to confirm alignment and coding distinctions in order to clarify codes [16]. Second, using a thematic approach [44], researchers will analyze the coded transcripts to identify SOAR preferences and usability themes as an iterative process. An additional comparative analysis based on age was conducted to identify any distinctions [44-46]. These discrepancies will be resolved by agreement during research team discussions.

After SOAR has been tailored, in aim 2, we will conduct a pilot study of the intervention using a 1-arm design to determine feasibility, acceptability, willingness, and safety for transgender women (SOAR study design; Figure 1). Also, we will collect data on ART adherence (viral load) and relationship communication to establish a preliminary understanding of outcomes and implementation of measures in a larger study.

We will recruit transgender women (N=20) living with HIV and suboptimally adherent to ART (missed at 2 doses over 2 weeks), to complete the intervention. Additionally, participants must have been in a romantic relationship with a man for more than 1 month and live in Eastern Cape. For screening, participants will complete a rapid HIV viral load test to confirm HIV status.

There will be 5 participants per group for a total of 4 groups. All participants will be recruited and screened into the study by the trained study coordinator, and all recruitment activities will occur at transgender community–focused events. During the consent process, participants will be provided a general overview of the study and informed about the number of study sessions and expected behavioral and biomedical data collection procedures. As in aim 1, all participants will receive a travel reimbursement and refreshments.

We will use the same measures as outlined in the parent study to include feasibility, behavioral outcomes for ART adherence and relationship communication, and HIV viral load.

For this study, aim 1 procedures have been reviewed and approved by the University of Cape Town Review Board (FWA00001938) with reliance on the institutional review board at Arizona State University (STUDY00014539). For aim 2, the study procedures were reviewed and approved by the University of Pretoria Review Board (189/2022) with reliance on Arizona State University (16397). All participants completed written informed consent. All participants will complete written informed consent and will receive R150 (around US $10) as travel reimbursement for completing the study activities and an R150 (around US $10) data plan to support their session attendance. All data will be anonymized when reported.

The SOAR intervention for transgender women is responsive to South African clinical guidelines for HIV care and addresses barriers to HIV disclosure management and treatment with partners [67]. Specifically, recent clinical guidelines outline a recommendation to deploy mHealth tools for treatment support, as these may allow transgender women to navigate perceived and enacted stigma and discrimination more easily when seeking clinic care [15,16]. Given the established smartphone use in South Africa, and among transgender women, harnessing these tools in HIV interventions is feasible [68]. However, few mHealth HIV interventions have been designed and tested for transgender women [4].

SOAR leverages videoconferencing and group format for delivery. Both modes of delivery have been shown to be highly effective in other settings [69,70], and more research is needed to determine its feasibility with transgender women in South Africa. Further, SOAR has the potential to improve skill-building for HIV status disclosure management that may in turn garner needed support from partners and improve HIV treatment adherence. If partner disclosure and support are not feasible, then SOAR provides participants with coping skills to manage HIV treatment and identification of other support systems for care.

Given that transgender women have some of the highest HIV incidence rates in South Africa and globally [4], it is imperative that we develop more intervention options based on their lived experiences. Integrating mHealth tools into these interventions can empower participants, as it allows them to control engagement based on their safety and needs. If SOAR is feasible as videoconference delivery for transgender women, then we will propose an efficacy study of the intervention to understand the impact on HIV viral load and quality of life. The intervention has the potential to build relationship skills around HIV treatment for transgender women and their partners who are consistently left behind in the HIV response.

The one potential study limitation is smartphone ownership or access. Specifically, although smartphone use is high in South Africa, device costs may be prohibitive for some participants. To facilitate participation such that we have representation of transgender women across socioeconomic standing, we will provide smartphones for participants to borrow, or they may access a tablet with headphones at a community site to attend the sessions.