Consensus Building on Strategies That Address Medical Mistrust to Better Engage Priority Populations in HIV Cure Research

Abstract

Poor diversity within HIV cure-related trials has been attributed to medical mistrust. Therefore, we sought to identify strategies to overcome medical mistrust to increase participation in HIV cure research in the United States. We used a hybrid Delphi consensus-building process with a panel of multidisciplinary experts in HIV cure research (n = 54). The panel completed three surveys over time. The panel was organized into six groups: community members/experts; biomedical researchers; HIV care providers; funders and private industry members; bioethicists, regulators, and institutional review board members; and socio-behavioral scientists/medical mistrust experts. Forty-eight of the 54 panelists completed all three surveys. In round one, the panel provided qualitative responses on strategies to overcome medical mistrust. These responses were organized and, in subsequent surveys, listed as unique strategies that were ranked from most to least important, arriving at consensus. Across the six groups, the top-ranked strategy was “[connecting] eligible participants with people with HIV who have participated in [HIV cure trials] and are willing to share experiences (both positive and negative).” Another top-ranked strategy was to “engage in active listening to ensure that all questions and concerns presented by… eligible participant[s] are addressed [and] build trust and rapport.” Rankings varied slightly between groups. Investigative teams could prioritize peer-to-peer interactions to overcome medical mistrust and promote participation in novel HIV cure research.

Introduction

In the United States, HIV continues to disproportionately affect people from racial and ethnic diverse backgrounds, as well as transgender women.^1,2 In 2020, Black/African American individuals were 7.8 times more likely to be diagnosed with HIV than their White counterparts³ and in 2022, accounted for 37% of new HIV diagnoses but represented 12% of the population.¹ In 2019, transgender people, especially Black/African American transgender women, accounted for 46% of new HIV diagnoses while Latina transgender women accounted for 35%.² Year after year, the greatest burden of HIV falls on underrepresented groups.

At the same time, the field of HIV cure science is rapidly advancing. Much like the roll out of HIV advancements over the years, again, the populations enrolled in HIV cure trials do not reflect the characteristics of people carrying the greatest burden of HIV. One landscape analysis of HIV cure trials implemented in 2019 found that participants were 53% White, 32% Black/African American, 12% Hispanic, and 5.5% Asian, with only 11% of cure trials representing women.⁴ The lack of representation in HIV cure research limits the generalizability of research findings and may further exacerbate inequities in acceptability and uptake of newer and longer-term HIV suppression interventions that HIV cure research seeks to identify.^5–7

Currently, HIV cure research aims to either eliminate HIV from the body or achieve viral suppression in the absence of antiretroviral treatment (ART).⁸ Many HIV cure trials are early-stage and may require participants to pause their ART adherence to assess the effectiveness of potential cure strategies, via an analytical treatment interruption (ATI).⁹ While ATIs are closely monitored, the length of the interruption varies and poses moderate risks, including those associated with becoming virally unsuppressed. Thus, participants face the risk of onward transmission and potential anxiety associated with the breakdown of the U = U (undetectable = untransmittable) equation.^10–12 Given these possibilities, people with HIV (PWH) may have concerns about HIV cure trial participation, which intersects with medical mistrust, particularly when combined with the need to pause ART.

Poor diversity within HIV cure trials has been attributed to medical mistrust, which is defined as the propensity to lack trust or have suspicions of medical systems and personnel that may not prioritize the patient’s best interest.^13,14 A related concept, medical distrust, stems from a personal or collective experience wherein trust was violated, which can heighten anxiety and suspicion.¹⁴ Currently, there is no clear approach to address the legacies of maltreatment of racial and ethnic communities in medical institutions and in research, which are barriers to research participation. A qualitative study that applied critical race and intersectionality theory to the experiences of Black/African American and Hispanic/Latinx PWH revealed that participants were aware of structural racism and social inequality from overt discrimination or microaggressions and perceived the healthcare system as reflective of these inequities.¹⁵ Despite this awareness, participants expressed a strong desire to engage with healthcare.

An individual’s reluctance to risk negative experiences with healthcare providers highlights how medical distrust can often hinder, but not entirely prevent, engagement with HIV research.¹⁵ Though not specific to HIV cure trials, most PWH express a desire to participate in clinical trials if given the opportunity. Despite fear and distrust of clinical research, their motivation stems from a deep level of altruism.^16,17 The social-ecological model is a multi-level framework that details the interactions of individual (intrapersonal and interpersonal), institutional, community, and policy factors.^18,19 Addressing medical mistrust and distrust requires thoroughly comprehending how multiple levels may influence participants’ experiences within research settings.¹⁹

To date, evidence on effective strategies to overcome medical mistrust in HIV cure trials is limited. One qualitative study explored Black transgender women’s perceptions of transgender women’s participation in ATIs.²⁰ The study highlighted participants’ skepticism about being viewed as “test subjects”; distrust of researchers’ disclosure of HIV cure trial participation risks; doubts about medical providers’ commitment to providing care in case of complications; and hesitancy to disrupt undetectable viral load status. Recommendations centered on respecting individual dignity and autonomy and on building rapport with community members^.20 In addition, the United States Food and Drug Administration (FDA) recently proposed guidelines to diversify clinical trials by documenting demographic information, eliminating inclusion/exclusion criteria that are not scientifically justified, listing enrollment goals (e.g., by race/ethnicity and sex/gender), and designing study visit schedules that allow for working adults and caregivers to participate.²¹ Such guidance may further encourage the participation of traditionally underrepresented groups in ATI trials, indirectly influencing participants’ trust levels in clinical research settings. However, despite these advances, there remains limited guidance and no consensus on which concrete strategies should be prioritized by HIV cure research teams to address medical mistrust and improve participation of underrepresented groups in studies involving ATIs.

Our study sought to generate consensus on strategies to overcome medical mistrust in HIV cure research involving ATIs with a focus in the United States. We surveyed a multi-disciplinary expert panel using an iterative, consensus-building process. Ultimately, we aimed to identify actionable solutions to the issue of inadequate demographic representation in HIV cure trials.

Methods

The Delphi consensus-building panel data collection and analysis procedures are detailed separately.²² Our approach draws considerably from existing Delphi consensus-building literature.^23–28 The Delphi panel consisted of 54 participants, who completed 4 rounds of surveys, administered via Qualtrics^XM (Table 1). These were organized into 6 groups of experts, 48 of whom completed the Round 3 survey from which our findings are derived. The 6 expert groups were: (a) community experts and members, (b) biomedical researchers, (c) HIV care providers, (d) funders and private industry members, (e) bioethicists, regulators, and institutional review board (IRB) members, and (f) sociobehavioral scientists/medical mistrust experts (Table 2). An eight-member independent community consultation group reviewed selected results between each round in online focus groups. Findings from each survey round informed the content and design of subsequent instruments.

Table 1.

Delphi panel demographic characteristics (U.S. 2023–2024).

Characteristic	n	%
Gender identity
Cisgender woman	34	63.0%
Transgender woman	2	3.7%
Cisgender man	15	27.8%
Non-binary or gender queer	2	3.7%
Unknown	1	1.9%
Sex assigned at birth
Female	35	64.8%
Male	19	35.2%
Ethnicity
Hispanic or Latina/o/x	7	13.0%
Not Hispanic or Latina/o/x	46	85.2%
Unknown	1	1.9%
Race
Asian	6	11.1%
Black / African American	11	20.4%
White / Caucasian	32	59.3%
Mixed / Other	3	5.6%
Prefer not to answer	1	1.9%
Unknown	1	1.9%
Education level
High school diploma or GED	1	1.9%
College graduate	10	18.5%
Master's degree or equivalent	8	14.8%
Doctorate degree or equivalent	35	64.8%
US residence region
Northeast	19	35.2%
Southeast	8	14.8%
Southwest	1	1.9%
Midwest	2	3.7%
West	23	42.6%
Prefer not to answer	1	1.9%
Number of years worked in field (mean)	19.7
1 to 10	8	14.8%
11 to 20	21	38.9%
21 to 30	17	31.5%
31 to 40	5	9.3%
41 +	2	3.7%
Prefer not to answer	1	1.9%
Number of years in HIV cure-related research (mean)	7.9
0	9	16.7%
1 to 5	13	24.1%
6 to 10	19	35.2%
11 to 15	4	7.4%
16 to 20	2	3.7%
21 +	4	7.4%
Prefer not to answer	2	3.7%
Unknown	1	1.9%
Sample size	54

Table 2.

Panel composition of delphi groups.

Group	Starting N	Round 3 N	Description
A	16	15	Key persons that represent the perspectives of PWH across spectrums of age, sex and gender, race and ethnicity, and regions of the United States
B	8	6	Biomedical HIV cure researchers in the Advancing Clinical Therapeutics Globally (ACTG) Network and HIV cure research other groups that have utilized analytical treatment interruptions in the past 5 years.
C	8	9	HIV primary care providers (including those not involved in HIV cure research). Inclusion of HIV primary care providers is important to ensure analytical treatment interruptions remain acceptable, and this group has been underrepresented to date.
D	8	4	Funder and industry representatives who provide funding to support HIV cure research.
E	8	7	Bioethicists, regulators and Institutional review board members who may review HIV cure research.
F	8	7	Individuals studying medical mistrust, medical racism, and community engagement (sociobehavioral scientists/medical mistrust experts).
Total	56	48

We designed a 4-round Delphi survey study to improve engagement of underrepresented populations in HIV cure research involving ATI. In this manuscript, we report the final consensus ranking of strategies to address medical mistrust, which was achieved after Round 3. We used data from Rounds 1 and 2 to generate and refine the strategy options that we advanced to the Round 3 rankings. Below is a summary of the procedures.

Round 1 consisted of an open-ended questionnaire on approaches to reduce medical mistrust in HIV cure research, with an emphasis on trials requiring analytical treatment interruptions (ATIs). The survey provided brief definitions of medical mistrust (a person’s general uneasiness with healthcare and science, or the belief that their needs and interests are perceived to be inferior to those of the clinician or researcher) and trust in healthcare and scientific settings (the belief that the clinician or researcher is working with the participant’s best interests at heart). Participants responded to seven open ended questions about perceived trust, HIV cure research information sources, who holds responsibility for addressing mistrust, and best practices in trust building. We analyzed qualitative, open-ended responses using inductive content analysis, coding data into thematic categories, which the principal investigators (J.A.S and K.D.) reviewed for accuracy and consistency.

Round 2 survey questions were informed by Round 1 data and focused on potential solutions and strategies to overcome medical mistrust. Panelists received a summary of Round 1 findings and a list of eight strategies generated from Round 1 (Table 3). They were then asked to identify 3 out of 8 strategies they believed were most important (but not rank order as in 1, 2, 3). We summarized results using frequencies and proportions overall and by each of the six expert groups.

Table 3.

Round 2 proposed medical mistrust strategies, by group.

Group A Community Members and Experts	Group B biomedical researchers	Group C HIV care providers	Group D funders and private industry members	Group E bioethicists, regulators, and IRB members	Group F sociobehavioral scientists/ medical mistrust experts
Connect eligible participants with people who have participated in ATIs willing to share experiences Explore the basis of medical mistrust and directly address concerns Clearly explain precautions, policies in place to protect participants confidentially and concerns Meet people where they are: talk about competing priorities, how beneficial the study is/is not to participants	Provide nonjudgmental and objective advice surrounding realities of study participation Engage peer supporters to serve as participants navigators	Meet people where they are: talk about competing priorities, how beneficial the study is/is not to participants Provide nonjudgmental, and objective advice surrounding study participation in a way that centers person empowerment and agency Connect eligible participants with people who have participated in ATIs willing to share experiences	Engage in active listening (in your role) to ensure that all questions and concerns presented by your eligible participant are addressed, build trust and rapport Engage peer supporters to serve as participants navigators Explore the basis of medical mistrust and directly address concerns Provide nonjudgmental and objective advice surrounding realities of study participation	Engage peer supporters to serve as participants navigators Connect eligible participants with people with HIV who have participated in ATIs willing to share experiences Engage in active listening so questions and concerns are addressed, to build trust and rapport	Engage in active listening so questions and concerns are addressed, to build trust and rapport Provide nonjudgmental and objective advice surrounding realities of study participation

Note: Italics indicate responses tied for first place. Ties also affect other categories, resulting in 2 or 4 selections, rath.

Round 3 established the final consensus ordering reported in this manuscript. Panelists reviewed a summary of Round 2 results, and then were asked to ranked, from most (1) to least important (3), the three strategies advanced from Round 2: active listening to address questions and concerns and build rapport, exploring the basis of medical mistrust and directly addressing concerns, and connecting eligible participants with PWH who previously participated in ATI studies and are willing to share experiences, both positive and negative. We calculated ranked values for each strategy within each expert group and pooled responses across all panelists.

Ethics and informed consent:

The University of California San Diego, Institutional Review Board (IRB) approved this study (#805348). We obtained electronic informed consent from all participants before enrollment. Participation was voluntary, and panelists could decline or withdraw at any time without penalty. We de-identified all data before analysis and retained no personally identifying information.

Results

Of the 54 survey respondents, about two-thirds (63%) identified as cisgender women (Table 1). The majority were non-Hispanic/Latinx (85%) and White (59%), followed by Black/African American (20%) and Asian (11%). Virtually all had obtained at least a college-level degree (98%). Half of participants reported six or more years of experience in HIV cure research. Most had at least 10 years of experience in their respective fields (85%) (Table 2).

The recommended strategies to overcoming medical mistrust are presented in ranked order by group count (Figure 1). The pooled top-ranked strategy to overcome medical mistrust was “Connect eligible participants with PWH who have participated in ATIs and are willing to share experiences (both positive and negative).” The lowest-ranked strategy was “Explore the basis of medical mistrust and directly address concerns to ultimately alleviate or validate these worries.” In between, the second-place strategy was “Engage in active listening (in your role) to ensure that all questions and concerns presented by your eligible participant are addressed, build trust and rapport.”

Figure 1. Ranking of strategies to overcome medical mistrust.

Note. Values in bar graph label represent the number of panel groups (1–6) who ranked each of the proposed strategies from 1^st through 3^rd. Full description of proposed strategies:1. Connect eligible participants with people with HIV who have participated in analytical treatment interruptions (ATIs) and are willing to share experiences (both positive and negative experiences); 2. Engage in active listening (in the role of each panel member) to ensure that all questions and concerns presented by your eligible participants are addressed, build trust and rapport; 3. Explore the basis of medical mistrust and directly address concerns to ultimately alleviate or validate these worries.

Group-specific rankings show additional patterns (Table 4). While most groups recommended linking prior ATI participants with potential new ones, both (a) community members and experts and (c) HIV care providers considered this strategy their second choice. Instead, both these groups primarily recommended active listening and building rapport. Conversely, “engage in active listening” was the lowest-ranked choice for (b) biomedical researchers and (f) sociobehavioral scientists/medical mistrust experts. Interestingly, these two groups recommended exploring the basis of medical mistrust as their second-place recommendation – contrasting with the remainder of the sample, which ranked this strategy last.

Table 4.

Rankings of strategies to overcome medical mistrust (groups A-F).

	Proposed strategies
Groups	Connect participants with PWH who had ATIs	Engage in active listening	Explore basis of, and address concerns regarding, medical mistrust
D: Funders and Private Industry Members (n = 4)	Ranked #1	Ranked 2nd	Ranked 3rd
E. Bioethicist researchers (n = 6)	Ranked #1	Ranked 2nd	Ranked 3rd
B. Biomedical Researchers (n = 6)	Ranked #1	Ranked 3rd	Ranked 2nd
F. Socio-behavioral Scientists (n = 7)	Ranked #1	Ranked 3rd	Ranked 2nd
A. Community Members and Experts (n = 15)	Ranked #2	Ranked 1st	Ranked 3rd
C. HIV Care Providers (n = 9)	Ranked #2	Ranked 1st	Ranked 3rd

Note. Full description of proposed strategies:1. Connect eligible participants with people with HIV who have participated in analytical treatment interruptions (ATIs) and are willing to share experiences (both positive and negative experiences); 2. Engage in active listening (in the role of each panel member) to ensure that all questions and concerns presented by your eligible participants are addressed, build trust and rapport; 3. Explore the basis of medical mistrust and directly address concerns to ultimately alleviate or validate these worries.

The greatest variability in ranking is evident for the strategy listed as “engage in active listening.” Two groups each ranked it as their first choice: (a) community members and experts and (c) HIV care providers); second: (d) funders and private industry members and (e) bioethicists, regulators, and IRB members); and third: (b) biomedical researchers and (f) socio-behavioral scientists/medical mistrust experts.

Discussion

Our multi-disciplinary expert panel recommended connecting eligible participants with PWH who have completed an ATI as the primary solution to overcoming medical mistrust. Somewhat surprisingly, exploring the basis of medical mistrust was deemed as the overall lowest-ranked priority. The value of prioritizing “active listening” varied by respondent expertise group: respondents who work more closely with individuals (community members and HIV care providers) considered this the top-ranked strategy, while biomedical researchers and socio-behavioral scientists prioritized this last. As seen in the socioecological model, there is an interplay between interpersonal, institutional, structural, and systemic levels that affect the dynamics between participants and research/clinical settings. Our strategies to better engage underserved groups, align and interact with the multiple levels found in the socioecological model synergistically working to create an environment that is reflective of future participant needs.

Connecting eligible participants with PWH who have completed ATI trials can ease justifiable worries, preconceived notions, and fears regarding ATIs. Further reinforcing our findings, our independent community consultation group emphasized the need for the “meaningful involvement of PWH” as a vital strategy to engage both cisgender and transgender women in HIV cure trials.²⁹ The independent group highlighted the importance of leveraging the experiences of PWH who reflect priority populations as trusted messengers, educators, and more. They hold a wealth of knowledge and lived experiences that can aid research initiatives and offer support as peer research associates (PRAs) – people who share similar experiences with (potential) participants. Research on harm reduction and addiction that focuses on community involvement is increasingly including members from affected communities as Peer Research Associates (PRAs).³⁰ The involvement of PRAs has been shown to improve community trust, while enhancing the recruitment of underrepresented populations.^31,32 In HIV cure trials, establishing the connection between a PRA and an eligible participant could lead to open discussions about perspectives and concerns surrounding ATIs, allowing eligible participants to make informed decisions about research participation. However, research on sustainably involving PWH – via compensated research positions – is lacking.³³ Our findings suggest an opportunity to explore involving prior ATI participants as PRAs alongside research teams, to support eligible ATI participants through increased trust and engagement.

Our overall second-ranked strategy recommended engaging in active listening to create trust and rapport. Community members and HIV care providers ranked this response as their top strategy. HIV care providers and community members collaborate with PWH routinely and thus understand their priorities more closely.³⁴ This includes the shared goal of increasing the quality of life of PWH, achieving this through high quality care, consistent engagement and trust.³⁵ During HIV cure studies, providers can be informed of the patient’s participation and be an advocate for them, ensuring their concerns are heard. Conversely, biomedical researchers ranked this strategy last. However, it is essential for research teams to engage in active listening to help demystify fears, address knowledge gaps, and directly discuss medical mistrust worries. Research teams play a vital role in creating a welcoming and safe environment for research participants. Listening attentively to participants as they discuss their worries can lead to positive study improvements, such as adapting the study to meet the needs of the participants. As a case in point, a qualitative study of participants in a novel combination HIV cure trial found that participants’ trusting, long-standing relationships with the research personnel facilitated the decision to participate and mitigated worries throughout the study.³⁶ Both clinical and research teams should ensure that participant input is at the forefront of the issues being investigated. This intentional collaboration and open dialogue can demonstrate the study team’s focus on participant-centered research.

The lowest-ranked strategy among the top three responses was exploring the basis of medical mistrust. Our study shows that exploring the basis of medical mistrust is less of a priority than acknowledged in the literature. This is likely because respondents may have seen this strategy as less pragmatic or outside the scope of their responsibilities. While we assume all understood the need to acknowledge historical trauma and present-day healthcare inequities that have reaffirmed medical mistrust, and continue to propagate healthcare inequities, the broad nature of this strategy may have diffused any specific ideas about how to address historical trauma and maltreatment in research.³⁷ Our findings indicate that while potential participants may rightfully be distrustful of institutions associated with past harms, study teams may be more effective in overcoming mistrust by having open discussions about participants’ perceptions and past harms.

Medical mistrust persists due to chronic exposure to mistreatment, healthcare inequities, and structural racism. This has resulted in the underrepresentation of priority populations in some of the most well-funded and high-priority research areas.^32,33 At the interpersonal level, it is important to collaborate with individuals who have participated in past trials, as well as with community members who can share their lived experiences. This collaboration can help better engage future participants in HIV cure-related studies. While we have aggregated medical mistrust into a single concept, it is nuanced and varies based on the demographic, socioeconomic, and intersectional characteristics of those experiencing it. Further research is needed to holistically address medical mistrust, it is essential to view it as a multilayered issue in healthcare and HIV cure trials.

Lastly, we acknowledge that within the socioecological model, these strategies are categorized as individual level, rather than strategies aimed at institutional or systemic change. Although these are interpersonal strategies, the socioecological model highlights the way factors such as community, physical, social, and political environment inform one another.¹⁷ This interplay was noted by our panel members in the very first round of our survey effort. Many participants emphasized the complexities of medical mistrust, overcoming which could catalyze change in healthcare policies that support minoritized communities across healthcare settings, including HIV cure trials with ATIs. Further research is needed to better understand medical mistrust on a structural level, by analyzing the historically racist frameworks embedded in healthcare institutions that have exacerbated health disparities.

We acknowledge several limitations. First, given our methodology, we limited third-round response options to three choices. Other solutions, such as those ranked lower in second-round response items, may also represent effective means of addressing medical mistrust and could be explored further. Second, we acknowledge potentially limited generalizability. Our results are drawn from responses of a survey panel consisting of about 50 highly educated topic experts; while we oversampled cisgender women, only two participants identified as transgender women, two as nonbinary or gender queer; and more than half identified as White. Since these respondents were recruited through the authors’ United States-based scientific and community networks, survey responses and sample demographics may vary considerably in potential replication studies. Third, as addressed in our methodological work,²² group category membership may not be mutually exclusive. Specifically, in the third-round survey, three group (f) participants (socio-behavioral scientists/medical mistrust experts) identified as group (a) (community members and experts), and two group (b) participants (biomedical researchers) identified as group (c) (HIV care providers). This misclassification, though corrected in the analysis, has implications for the validity of group-based comparisons.

Conclusions

We explored strategies to overcome medical mistrust in HIV cure research with ATIs in the United States by surveying a multi-disciplinary panel of experts as part of an iterative, consensus-building process. Connecting eligible participants with prior ATI participants willing to share experiences emerged as the top-ranked strategy. Our findings suggest that addressing the historical basis of medical mistrust may be less of a priority than documented in existing literature. While potential participants may understandably lack trust in institutions associated with past harms, investigative teams should consider prioritizing peer-to-peer interactions within ATI studies while addressing ethical implications.

PUBLIC HEALTH SIGNIFICANCE.

Medical mistrust undermines diversity in HIV cure trials. This study identifies consensus strategies to address mistrust, emphasizing peer-to-peer engagement and active listening, offering practical guidance to improve equitable participation of populations most affected by HIV in cure-related research.