Perceptions of Risks and Benefits of Participating in HIV Cure-Related Research Among Diverse Young Adults Living with HIV in the United States: Qualitative Research Findings

Introduction

In 2018, young adults between 25–29 and 20–24 years of age had the first and second highest HIV infection rates, according to the U.S. Center for Disease Control.¹ Furthermore, young adults are the least likely to be aware of their infection, are less engaged in HIV care, have lower viral suppression rates, and are less represented in HIV research compared with older adults.^2–6 As the high incidence of HIV among young people persists, and older people living with HIV (PLWH) continue to age and become ineligible for participation in HIV cure studies, young adults living with HIV (YLWH) will be spearheading decision-making related to HIV cure research studies. However, there is dearth of data on their perspectives on HIV cure research.

Although antiretroviral therapy (ART) has sustained the lives of millions of PLWH worldwide, high levels of ART adherence remain low.^7,8 Biomedical research toward an HIV cure is rapidly advancing and targeting the outcome of ART-free sustained viral suppression. As of March 2022, 250 interventional and observational studies for HIV cure were being conducted worldwide.⁹ Although little is known about the perceptions of risks and benefits involved in current HIV cure research, which are notable, the extant literature has largely focused on older PLWH.^10,11 Perceptions of the risks and benefits toward different HIV cure research approaches vary based on age. For example, participants younger than 50 years of age were more likely to be demotivated by perceived social risk [e.g., stigma, discrimination, fear of HIV transmission during analytic treatment interruptions (ATIs; ART interruption to assess HIV remission)] compared with those older than 50 years.¹²

Owing to their age, perception of risks and benefits of YLWH toward HIV cure research, ATIs, HIV disclosures, and HIV-related stigma may drastically differ from older PLWH. In addition, YLWH may have different levels of trust toward medical establishments and altruistic attitudes toward participating in HIV research versus older PLWH who have lived through a historically different period of time.¹³ Furthermore, given the advancements in ART, YLWH have a different experience from older PLWH regarding ART because YLWH have benefitted from newer ARTs that have lower dosing frequency and fewer adverse effects. Some YLWH do not perceive cure strategies to be better than their current treatment.^12,14 These differences in perceived risks and benefits between YLWH and older PLWH warrant further investigation to understand how factors such as stigma, moral obligation to participate, and experiences with HIV medications can explain these differences.

Although YLWH will likely be most directly affected by future cure interventions, as they become available,^12,13 currently available research on the perceived risks and benefits of HIV cure research may not be representative of young adults who share notably different views of HIV cure research.^13,15 Future HIV cure research must include more perspectives from racial and ethnic diverse populations—who have been disproportionately affected by HIV¹—and younger populations who will make up participant pools for future research. Engaging and recruiting younger populations into novel HIV cure studies will require an understanding of their motivations for a cure and perceived barriers to research. Therefore, we conducted semistructured one-on-one qualitative interviews with diverse YLWH to gain insights into the perceived motivators and barriers to participation in HIV cure research.

Materials and Methods

Results

From August to October 2020, we interviewed a select group of diverse 20 YLWH (Table 1). Participants had a mean age of 25.7 years (SD = 2.6), and mostly identified as male (65%), Black race (25%), gay (50%), and living in the Western region of the United States (65%). Three individuals (15%) were HIV diagnosed at birth. Approximately 55% of participants had experienced financial instability.

In general, most participants reported not knowing anything specific about HIV cure research except news article headlines (e.g., the “Berlin patient”). When asked about what comes to mind when they hear the phrase “HIV cure,” participants' responses generally fell along “clinical impact” or “personal benefits” categories. Clinical impact responses were summarized as “going beyond undetectable,” “becoming negative again,” virus is “dormant,” “giving the immune system a break,” “completely resolve,” or “eliminate” HIV. Examples of the personal benefits responses included: “No longer living with the complications of HIV”; feeling hopeful; relief from taking medications, doctor appointments, and insurance issues; having less stress and stigma; and no longer having to disclose HIV status. Main interview themes included (1) facilitators of HIV cure research participation, (2) barriers to HIV cure research participation, (3) ATI perspectives and concerns, and (4) what young adults should consider before participating in HIV research. Figure 1 provides key themes and subthemes of the interviews.

Discussion

To our knowledge, this is the first socio-behavioral study on perceptions of HIV cure-related research to focus exclusively on YLWH. We found wide-ranging perceived motivators and barriers to participation in HIV cure research among interviewees. First, very few participants had ever heard of HIV cure-related research, and several of them raised important questions around trading established treatment and care routines versus the uncertainty of participating in HIV cure-related research. Although most were engaged in care, few had little prior awareness of HIV cure, one of the most important priorities for the National Institutes of Health,²⁰ which reveals a clear need for further education and outreach on HIV cure research.

Second, many YLWH expressed ideas regarding altruism and research participation. Although narratives about giving up their bodies to science or to advance a cure have been documented in studies with older populations,¹¹ including in the end-of-life studies,²¹ we have yet to find these narratives among YLWH. Third, despite having exclusively experienced ART with low pill burden and few adverse effects, most participants were eager to receive an HIV cure without the consideration of any upper thresholds of acceptable risk. Fourth, psychological distress was a prominent theme that was expressed by nearly all participants as a barrier to participation in HIV cure research. Finally, most participants expressed fear or concern over the seemingly contradicting messaging between undetectable = untransmittable^22,23 and need for ATIs. ATIs were particularly concerning for YLWH who had acquired HIV perinatally.

The majority of YLWH in our study had not previously heard of HIV cure-related research. This finding is consistent with prior focus groups conducted among predominantly older Black/African Americans in the United States.²⁴ When probed about an HIV cure, participants also conceived of a cure as completely resolving or eliminating HIV, or relief from HIV medications, corroborating results from earlier studies in older adults living with HIV.^14,25,26 Of interest, there were additional insights gained by some YLWH. For example, some viewed benefits of a cure as not having to live with HIV complications, taking ART, attending doctor appointments, dealing with insurance issues, as well as having less stress, stigma, or fear of disclosure. An important caveat is that HIV cure research participation may require more frequent clinic visits to monitor safety (e.g., HIV viral load rebound).²⁷ For YLWH who have benefited from the availability of potent ART, it will be important to adequately manage expectations about when efficacious HIV cure-related regimens would be available.²⁸

In addition, participation in HIV cure trials that require ATIs may also place YLWH in situations where they have to disclose their participation to sexual partners.²⁹ This is because with ATIs, there are extended periods of time where participants are off ART and may experience viral rebound.²⁷ Having sufficient support regarding disclosure processes, PrEP for sexual partners, and counseling are services being considered necessary for HIV cure research,²⁹ which were also echoed in our data.

Of interest, although 55% of young participants in our study reported being financially unstable, compensation did not surface as a strong theoretical motivator to participation.^30,31 However, altruism emerged as an important facilitator for HIV cure research participation among YLWH, concordant with previous research on willingness to participate in older adults^32,33 and accounts from prior trial participants.^34,35 Of importance, engagement and recruitment efforts around HIV cure-related research will need to be focused on long-term scientific and societal benefits of participation.³²

The social implications of participation—including reducing stigma—emerged as an important motivator, which is also consistent with prior research conducted among diverse women living with HIV in the United States,³⁶ as well as research on theoretical willingness to participate.^25,37 What will be important to consider for future purposes is the nuanced issue that current HIV cure strategies under investigation are not completely eliminating HIV from the body, and thus, whether YLWH would view themselves as free of stigma and disclosure requirements.¹¹ More research will be necessary to understand how HIV cure research participation, particularly ATIs, affects both internal and external stigma in YLWH.³⁸

Most YLWH viewed physical side effects as a barrier to participation, congruent with prior sociobehavioral sciences research showing high thresholds of safety would be necessary for HIV cure-related research interventions to remain acceptable to diverse PLWH.^14,39 In our study, the potential for long-term toxicity or opportunity costs of participating in earlier studies (vs. later studies when interventions may show more efficacy) did not emerge as important topics, but we suspect these considerations will remain important for YLWH. Ethically problematic was a subset of participants who did not place any upper thresholds of acceptable risk in their calculation whether to participate.⁴⁰

An important finding in our study was the frequently discussed psychological distress that may be associated with HIV cure research participation. The possibility of developing or exacerbating depression, stress, anxiety, and trauma emerged as important concerns, and underscored the urgency of incorporating mental health assessments and counseling and support interventions to address psychosocial needs during trial participation.^14,38 In particular, ATIs have been associated with anxiety in both theoretical^41,42 and actual³⁴ HIV cure-related research with older PLWH. The mention of emotional trauma around being let down if a cure regimen did not work was a salient one. Prior participants have expressed disappointments following relapse of virus.⁴³

Additional deterrents included the potential for HIV status disclosure and the social risk of being recognized as someone living with HIV. Ethically, HIV cure research teams must have robust confidentiality protections for PLWH participating in this research.⁴⁴ Logistical aspects such as time commitments and transportation should also be taken into account.³⁶ While structural racism and discrimination did not emerge as major themes in our study, we acknowledge that these issues remain critically important in decisions to engage in biomedical research, particularly for Black/African American PLWH, and will need to be further explored.⁴⁵

Other barriers to HIV cure research participation were framed in terms of concerns around trading a known treatment and care routine with uncertainty. This is a salient finding, because ART adherence has traditionally been a challenge for YLWH.⁴⁶ This perceived contradiction between the need for ART adherence and trial designs that require disruptions in ART have been noted elsewhere.^{24,26,42,47,48} This finding is also consistent with results from older Black/African American individuals who reported being satisfied with life on ART.²⁴ Participants who acquired HIV perinatally discussed their content with continuing taking their current medication given the duration of time that they have lived with HIV and not knowing a life without HIV.⁴⁹ The perceptions of YLWH who acquired HIV perinatally may also more closely align those of long-term survivors who have experienced a long journey toward becoming virologically suppressed.

The need for robust partner protection measures also appeared paramount for YLWH, including PrEP and condoms for sexual partners, consistent with prior research.^47,48 Although consensus has not been achieved on acceptable risk mitigation packages for sexual partners of ATI trial participants, various approaches have been proposed.^29,50 These are also ethically relevant and align with the principle of nonmaleficence. Finally, a topic that was unexplored in our study was the need to integrate HIV and reproductive health services for YLWH, particularly women living with HIV.^51,52

Our research is limited in that we captured the voices of 20 diverse YLWH from across the United States; however, owing to this relatively small sample size, our results may not be generalizable to all YLWH, especially those in other countries. There are currently no published studies comparing hypothetical and actual willingness to participate in HIV cure studies; therefore, it is unknown how results from this study will translate into actual study participation. However, we believe that these data can help shed light on motivators and deterrents of YLWH to participate in HIV cure trials and allow researchers to consider strategies to minimize low participation and retention rates.

Conclusions

YLWH remain vastly under-represented in HIV cure-related research and are less engaged in HIV care than older adults; yet will be key decision-makers in advancements of the HIV cure agenda in years to come.¹³ It will be critical to involve a new generation that is less engaged in research and did not witnessed the early days of the HIV epidemic, while carefully managing expectations around scientific advancements. Optimizing engagement, recruitment, and retention efforts around HIV cure-related research will require involvement of young people of color in all aspects of clinical trials.^13,53 Given the need for more social sciences research in this area, we have and will continue to use the results from this study to inform a larger survey of YLWH in the United States to further explore interest in participating in HIV cure research. Similar research will also be important in international contexts as more trials are set to begin in low- and middle-income countries in years to come.⁵³

Supplementary Material

Authors' Contributions

P.S.: conceptualization, methodology, formal analysis, investigation, resources, writing—original draft, writing—review and editing, supervision, funding acquisition; C.K.C.: methodology, validation, formal analysis, data curation, writing—original draft, writing—review and editing, visualization, project administration; J.A.S.: conceptualization, writing—original draft, writing—review and editing; S.N.: writing—original draft, writing—review and editing, visualization; K.D.: conceptualization, validation, formal analysis, writing—original draft, writing—review and editing, funding acquisition.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

Research reported in this publication was supported by the National Institute of Mental Health under award numbers R21 MH122280 (Multiple Principal Investigators P.S. and K.D.).

Supplementary Material

Supplementary Data S1