Over the past 2 decades, transgender individuals, particularly Black and Latina transgender women, have received increasing attention within HIV research [1-9]. Such research has consistently documented the pervasive role stigma plays in creating and sustaining health inequities among this population. However, this research proliferation has also raised questions about practices that may unintentionally stigmatize or retraumatize the very communities they are designed to benefit [4,10-15]. One area of particular concern is the measurement of stigma as part of HIV-related research with transgender and nonbinary individuals. First, there is concern that specific items within commonly used measures may unintentionally recreate or activate stigma. For example, many stigma and minority stress scales [16-19] include items that may be experienced as stigmatizing (eg, “Being transgender is disgusting to me”) [19] or ask participants to recount and relive traumatic experiences (eg, history of physical and sexual violence, family rejection, and experiences of discrimination and harassment) to document their association with negative affect or health behavior [2]. There has been considerable debate within the larger field of trauma-related research as to whether recalling and answering questions about past trauma has negative or positive consequences for study participants [20-29]. However, there is surprisingly limited research within HIV science on the potential emotional impacts of participating in stigma research. Second, there are no evidence-based guidelines for person-centered, trauma-informed, and actively destigmatizing implementation of HIV stigma research. Conducting stigma research is critical for generating accurate information about HIV epidemiology, risk and protective factors, and intervention strategies for transgender and nonbinary individuals. Yet little research has directly examined the experiences of transgender and nonbinary individuals when participating in these studies, or identified specific research practices (eg, recruitment materials or study framing, choice of specific survey measures, data collection protocols, and researcher behaviors) that may influence study participation, retention, and data quality [30]. Equally important, research has not adequately examined the potential for unintended harm due to emotional distress experienced by participating in such research and what specific strategies might mitigate against potential distressful research experiences.

Research documenting multiple and intersecting structural factors, including racism, sexism, transphobia, homophobia, and other systems of stigmatization, oppression, and traumatic victimization that contribute to the disproportionately high rates of HIV infection and HIV-related morbidity in this population [2-4,6,7,14,31-35]. One of the strengths of HIV research in this area has been its intersectional focus, [36] as well as the acknowledgement that stigma operates at individual, interpersonal, and structural levels. Intersectional approaches demonstrate the ways in which HIV-stigma and other sources of stigma occur simultaneously and interact to impact transgender and nonbinary individual’s daily experience, health outcomes, and engagement with care. Research suggests that transgender and nonbinary individuals may experience this impact as traumatic, and support trauma-informed approaches that seek to mitigate retraumatization within the provision of care [37-43]. Transgender and nonbinary individuals health disparities have been directly linked to intersectional and multidimensional stigma processes [37,41,44,45], underscoring the extent to which this approach is essential for advancements in transgender and nonbinary individual–specific stigma frameworks, measurement, and intervention development.

Within the fields of clinical psychology and neuroscience, there has been intense debate about the impact of research about traumatic experiences on study participants [20-29]. Some evidence suggests that such research might lead to traumatization or cause further harm to those with previous exposure to violence or abuse. One meta-analysis of studies about traumatic events found that approximately 25% (IQR 4.3%-50%) of adult participants reported distressing impacts (ie, unexpected upset, negative emotions, unwanted thoughts, or distress) as a result of research participation. Although, most people find that participating in trauma research is distressing, they also report that they find it worthwhile and meaningful [28]. Neuroscience research on memory reconsolidation suggests that the context and content of memory reactivation may determine its harmful or therapeutic impact. Data indicate that research participants anticipate or attribute negative impacts to study participation; in 1 large-scale study of traumatic experience, 94% of participants rated their participation as more than minimal risk, with participants that had greater previous exposure to trauma reporting higher levels of distress [46]. However, limited research within the field of HIV has directly examined the potential impact of stigma research itself on transgender and nonbinary participants.

Growing recognition of the importance of community partnership for HIV research with transgender and nonbinary individuals has led to a rise of studies that rely on community health centers or other service agencies for research recruitment and implementation [47-50]. It is well established that experiences of stigma within these settings may negatively impact transgender and nonbinary individual’s willingness to receive needed health care, including HIV testing, treatment, or pre-exposure prophylaxis [37-39,51,52]. If stigmatizing or harmful research is conducted within these settings, there is the potential to reduce transgender and nonbinary individual’s trust in the very organizations upon which they depend to access life-saving services. As such, it is essential to understand whether and under what conditions HIV stigma research may result in unintentional harm or stigmatization of transgender and nonbinary individuals, and how harmful impacts can be reduced.

Evidence indicates that mistrust of research projects, study teams, or settings leads to difficulties with recruitment and retention of study participants and may be associated with false or misleading responses to study measures. Studies indicate that research mistrust is particularly strong among transgender and nonbinary participants, who may report feeling used or mistreated within HIV research contexts [53-55]. In 1 study, transgender women reported that research scripts and procedures can be experienced as microaggressions [55]. Critical HIV-related stigma research is likely to underperform and fail to provide much needed data on stigma processes if participants are discouraged from participating or alienated from the research enterprise by perceptions that stigma research is itself stigmatizing [56].

Many HIV stigma studies report incorporating intentionally affirming components into their research practice, such as measures of self-esteem, community-connectedness, or other resilience factors [57,58]. However, there has been no systematic compilation of these strategies, or analysis of their potential use in reducing stigma experiences. This research gap results in a lack of consensus of what is meant by trauma-informed HIV stigma research, as well as gaps in how to best implement and evaluate stigma-reducing measures in HIV research practice. Outside of HIV research, there are models for patient-centered, trauma-informed health research [59] that could be adapted to better inform implementation strategies, but such adaptation needs to be grounded in empirical data from participants, researchers, and practitioners with direct experience in the field.

This study is based on an interdisciplinary integration of minority-stress and trauma-informed theoretical frameworks to explain health inequity. Minority stress theory [60] is a strong epidemiological framework for explaining disparity but is less precise in specifying mechanisms of an individual stigmatized person’s behavior, feelings, or experience. To complement this theory, we incorporate a conceptual framework developed specifically to support the mental health of TGNB individuals [61], which combines 2 trauma-informed care models to guide our research questions and analysis. The first, developed by Fallot & Harris [62,63], emphasizes five principles of interaction: safety, trustworthiness, collaboration, choice, and empowerment. The second, guiding principles of trauma-informed care created by the Substance Abuse and Mental Health Services Administration within the US Department of Health and Human Services, focuses on attention to cultural, historical, and gender issues that impact power relationships, privilege, and oppression [64]. This trauma-informed theoretical approach attends to the potential presence of trauma-related symptoms on the thoughts, feelings, needs, and reactions of TGNB research participants, and aims to actively disrupt retraumatization through the creation of interpersonal processes and settings that emphasize safety, trust, collaboration, empowerment, and choice. Rather than focusing on isolating and describing stigmatizing internal and external experiences that happen to a marginalized person, a trauma-informed approach to stigma research centers how those marginalizing experiences thwart a survivor’s wellness, healing, and resilience [65]. Trauma-informed approaches are, therefore, inherently person-centered, and strengths-based in that they entail recognition of the signs and symptoms of trauma in an individual’s behavior and guide clinical responses to minimize negative impact on the survivor’s natural recovery process [64]. These characteristics are likely to support greater engagement, quality, and benefit of HIV research among transgender and nonbinary individuals [55].

The primary aim of this study is to develop empirically informed, trauma-informed guidelines for conducting HIV-related stigma research with transgender and nonbinary individuals. This work seeks to address critical gaps in the field by improving recruitment, retention, and data quality while reducing the potential for harm during research participation. Specifically, the study focuses on the following aims. First, this study aims at understanding participant experiences by conducting in-depth interviews with transgender and nonbinary participants who have engaged in HIV or sexual health-related research to explore their experiences, including factors that contribute to or mitigate distress, stigma, and harm. This aim seeks to uncover the nuanced challenges and opportunities for designing research that supports participant well-being. Second, this study aims to gather stakeholder perspectives by conducting in-depth interviews with researchers and mental health clinicians to identify current practices, challenges, and strategies for implementing trauma-informed and person-centered approaches in HIV stigma research. This aim emphasizes understanding the perspectives of professionals who interact with transgender and nonbinary populations in research and clinical settings. Third, this study aims to develop and refine trauma-informed guidelines by using findings from the first and second aims to create a preliminary set of trauma-informed research guidelines. These guidelines will be refined through a modified Delphi process involving transgender and nonbinary individuals, researchers, and mental health professionals to ensure their relevance, acceptability, and applicability across diverse research contexts.

By integrating qualitative interviews with a structured consensus-building approach, this study aims to establish actionable and evidence-based recommendations. These guidelines will enhance the ethical rigor and methodological quality of HIV stigma research, contributing to improved health equity and reducing unintentional harm in research practices.

Our study is designed to address a critical gap in existing HIV stigma research with transgender and nonbinary individuals by examining experiences of stigma within the research context and identifying strategies for improving data quality and reducing unintentional harm in study recruitment, methodology, implementation, and dissemination. This study will engage in primary data collection using both qualitative and quantitative data collection methodology. To accomplish the study aims we will first, conduct in-depth interviews with transgender and nonbinary individuals (n=30) to better understand how they understand and experience participation in HIV-related stigma research, including willingness to respond to questions about stigma and factors that may contribute to or mitigate potential distressing or stigmatizing experiences within the research context. Second we will conduct in-depth interviews with 2 groups: investigators who conduct HIV-related stigma research with transgender and nonbinary individuals, to better understand perceptions of and experiences with conducting stigma research with transgender and nonbinary individuals and compile existing strategies for mitigating harm (n=15) and mental health professionals (n=15) who provide care to transgender and nonbinary individuals to better understand ways in which experiences of stigma can be measured and studies can be conducted in a manner that is person-centered, trauma-informed, and actively destigmatizing. Third, we will develop a set of empirically informed guidelines for conducting HIV stigma research with transgender and nonbinary individuals. We will use a modified Delphi technique to engage a panel of transgender and nonbinary individuals, mental health providers, and researchers in a consensus building process to identify practical recommendations for person-centered, trauma-informed recruitment, measurement, and conduct of HIV-related stigma research with transgender and nonbinary individuals.

The sample sizes for this study were designed to ensure robust data collection and meaningful analysis across all phases. For aims 1 and 2, the sample size was chosen based on recommendations for similar qualitative inquires to ensure thematic saturation and demographic diversity [66-69]. In aim 3 the Delphi panel will consist of 75 participants (25 transgender and nonbinary individuals, 25 researchers, and 25 clinicians), aligning with best practices for achieving reliable consensus and providing robustness against attrition [68,70,71]. These sample sizes ensured methodological rigor, demographic representativeness, and the capacity to develop empirically informed, trauma-informed research guidelines.

The interview guide was developed through a collaborative, trauma-informed approach to ensure that all protocols and procedures reflected the study’s goals and minimized potential harm to participants. This process involved a 3-step methodology with the transgender-identified research team. First, the team conducted an in-depth review of existing trauma-informed care models and adopted the framework developed by The Institute on Trauma and Trauma-Informed Care (ITTC) at the University of Buffalo, which emphasizes the principles of safety, choice, empowerment, collaboration, and trustworthiness. Second, components from ITTC’s Trauma-Informed Organizational Change Manual [73] were adapted and integrated into the research procedures, including participant recruitment, consent, interview data collection, and analysis, to align all research activities with a trauma-informed approach. Third, the interview questions, prompts, and scripts were mapped to the ITTC framework to minimize risks of retraumatization and ensure a supportive environment for participants. Interview questions were refined to align with the study’s 4 overarching research questions and tailored to the perspectives of the 3 participant groups, researchers, community stakeholders, and mental health clinicians, ensuring comparability and analytic integrity across the study phases (Multimedia Appendix 1).

Data collected in aims 1 and 2 will be analyzed using rapid qualitative analytic methods, [74-77] to identify key themes that best reflect the research decision-making process, perceptions and experiences of transgender and nonbinary individuals. We will assign four trained team members to summarize a subset of the interview transcripts independently, extracting key data into a summary template based on our framework and interview guide; triangulate key themes in the transcript through documenting observations, quotations, and reflections into the summary template; meet to compare and combine templates for each interview; and create a comprehensive matrix identifying common themes and contrasts across and within stakeholder groups.

In preparation for aim 3, we will use the themes that were identified in the qualitative interviews to develop a preliminary list of survey items for use in the first stage of the modified Delphi process (aim 3) [78]. The use of qualitative interviews in a pre-Delphi phase [78-80] allows for all relevant stakeholder groups to guide the Delphi process by contributing to the development of the first round Delphi survey. To ensure that the Delphi survey items describe and capture the perceptions and experiences of all the stakeholder groups participating in aim 3, we will develop items using the language and narratives participants use during their interviews [78,80,81]. For example, the language used to describe and the meaning behind core concepts within stigma research may differ distinctly between stakeholder groups and could contribute to inaccurate measurement and interpretation of research findings. By integrating language from each stakeholder group into the Delphi survey we hope to better reflect the experiences of all relevant stakeholders involved in this process [79,82,83]. We will then compare the themes and associations derived from Aims 1 and 2 to better understand areas of concordance and discordance between stakeholder groups [78-81,84]. For example, it is possible that interview findings highlight similar domains across participant groups that are key to understanding and improving stigma research procedures, yet what is important to address within these domains may differ by stakeholder group. The use of qualitative interview findings will help further parse out and include survey items that address this complexity.

This study addresses a critical gap in HIV-related stigma research by developing trauma-informed guidelines to improve the quality of research involving transgender and nonbinary individuals. HIV stigma research has historically documented the pervasive role of stigma in shaping health inequities but has largely overlooked the unintended harms participants may experience within the research process itself. By using an interdisciplinary, trauma-informed approach grounded in qualitative data collection and a modified Delphi method, this study emphasizes principles of safety, trustworthiness, collaboration, empowerment, and cultural sensitivity. The findings aim to enhance participant engagement, reduce emotional distress, and improve data quality, thereby advancing ethical and effective research practices. Through active collaboration with community members, researchers, and clinicians, this project provides a model for addressing stigma while centering participant well-being and resilience.

The study’s findings underscore the critical importance of adopting a trauma-informed approach to HIV stigma research with transgender and nonbinary individuals. Interviews with community members, researchers, and clinicians revealed the significant benefits of trauma-informed principles for enhancing participant trust, retention, and engagement while also improving the quality of collected data. Key findings include the following.

To make meaningful strides in stigma research, it is imperative to examine experiences of stigma within the research context and identify strategies to improve data quality while reducing unintentional harm in study recruitment, methodology, implementation, and dissemination. This study addresses these critical needs by developing empirically informed trauma-informed guidelines for conducting HIV-related stigma research with transgender and nonbinary individuals.

Grounded in interdisciplinary theoretical frameworks and extensive collaboration with transgender and nonbinary participants, researchers, and clinicians, this study highlights the transformative potential of trauma-informed approaches. These guidelines emphasize the principles of safety, trustworthiness, collaboration, empowerment, and cultural sensitivity, demonstrating their capacity to enhance participant engagement, foster trust, and mitigate risks of retraumatization. Findings further underscore the importance of systemic institutional support, including training programs, funding mechanisms, and policy revisions at the institutional level, to ensure the widespread adoption of these practices.

The study achieved its goals by developing and refining these guidelines through rigorous qualitative analyses and a modified Delphi process. By embedding trauma-informed principles into research methodologies, this work sets a new standard for ethical and effective research practices. These guidelines have the potential to increase researchers’ capacity to recruit and retain transgender and nonbinary participants in stigma research, improve the quality of collected data, and reduce the unintended harms of research participation.

Next steps include broad dissemination of the guidelines through community-friendly formats, workshops, and academic publications. These efforts will ensure that the findings are accessible to a diverse range of stakeholders, including researchers, clinicians, policy makers, and community organizations. By reshaping HIV stigma research methodologies, this work contributes to advancing health equity and ethical research practices, with implications for other high-priority populations and fields of health disparity research.