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IntroductionThe Last Gift study at the University of California San Diego (UCSD), United States enrolls terminally ill people with HIV (PWH) in HIV cure research.MethodsFrom 2017 to 2022, we conducted surveys with Last Gift participants and their next-of-kin/loved ones to evaluate willingness to participate in different types of HIV cure research at the end of life (EOL). We analyzed willingness data descriptively.ResultsWe surveyed 17 Last Gift participants and 17 next-of-kin/loved ones. More than half of Last Gift participants ( n  = 10; 58.8%) expressed willingness to participate in studies involving totally new treatments or approaches ('first-in-human' studies), a combination of different approaches, the use of unique antibodies, proteins or molecules, or therapeutic vaccines. Under one-quarter of Last Gift participants ( n  = 4; 23.5%) expressed willingness to participate in research involving interventions that may shorten their life expectancy to benefit medical research. Most Last Gift participants and their next-of-kin/loved ones also expressed high acceptance for various types of donations and biopsies at the EOL (e.g. hair donations and skin, lymph node or gut biopsies).DiscussionKnowing whether people would be willing to participate in different types of EOL HIV cure research can help inform the design of future innovative studies. As a research community, we have a duty to design studies with adequate safeguards to preserve the public trust in research and honor PWH's important gift to humanity.

BackgroundThere is limited systematic information available about the perspectives of participants enrolled in intensive combination HIV cure-related trials inclusive of an extended analytical treatment interruption (ATI).ObjectiveTo assess and understand experiences of people with HIV involved in a combination HIV cure-related trial with an extended ATI.MethodsThe trial included five interventions and was followed by an ATI lasting up to 52 wk. From 2022 - 2023, we conducted in-depth interviews with study participants following their extended ATIs. Interviews were audio-recorded, transcribed, and analyzed via conventional thematic analysis.ResultsWe interviewed seven participants. The majority were male, White, and non-Hispanic, with a median age of 37 years. Trust in the research team, scientific altruism and hope of becoming a post-intervention controller were key motivators for joining the trial. Interviewees reported being satisfied with their decision to participate in the trial and the extended ATI. Most recounted feelings of worry related to viral rebound during the ATI. Participants reported both defeat and relief with ART restart. Four faced challenges with protecting partners from HIV during their ATI, such as trying to find out if their partner(s) were using pre-exposure prophylaxis.ConclusionsOur findings demonstrate potential improvements for future ATI trial participant experiences, such as more robust resources for psychosocial support and partner protections. Dedicating greater effort to understanding participant ATI experiences can inform the design of future participant-centered HIV cure trial protocols.

Nearly half of new HIV cases in the United States are among youth. Little is known about the willingness of young adults living with HIV (YLWH) to participate in HIV cure-related research. In 2021, we recruited 271 YLWH aged 18-29 for an online survey. We asked questions about willingness to participate in HIV cure research, perceived risks and benefits, acceptable trade-offs, and perceptions on analytical treatment interruptions. We conducted descriptive analyses to summarize data and bivariate analyses to explore correlations by demographics. Most respondents (mean age = 26) identified as men (86%) and Black Americans (69%). YLWH expressed high willingness to consider participating in cell- and gene-based approaches (75%) and immune-based approaches (71%). Approximately 45% would be willing to let their viral load become detectable for a period of time during an HIV cure study, 27% would not be willing, and 28% did not know. The social risk most likely to deter participation was the possibility of transmitting HIV to sex partners while off HIV medications (65% of respondents would be deterred a great deal or a lot). Compared to the 25-29 age group (n = 192), the 18-24 age group (n = 79) was more likely to indicate that having to disclose HIV status would matter a great deal in considering participation in HIV cure research (38% vs. 21%, p = .003). Inclusion and engagement of YLWH are critical for advancing novel HIV curative agents. Our article concludes with possible considerations for engaging YLWH in HIV cure research. Physical, clinical, and social risks will need to be kept to a minimum, and research teams will need to proactively mitigate the possibility of transmitting HIV to sex partners while off HIV medications.

BackgroundWhereas national attention has been paid to the ongoing mental health crises among young people triggered by the COVID-19 pandemic, less is known about the social, physical and psychological impacts of COVID-19 on young people living with HIV, especially racial/ethnic minorities.SettingOnline survey of participants across the U.S.MethodA national cross-sectional survey of non-Latinx Black and Latinx young adults (18-29) living with HIV. Between April and August 2021, participants answered survey questions about several domains (eg, stress, anxiety, relationships, work, quality of life) that were worsened, improved, or unchanged during the pandemic. We ran a logistic regression estimating the self-reported impact of the pandemic on these domains between 2 age groups (ages 18-24 versus 25-29).ResultsThe sample size was 231 (186 non-Latinx Black, 45 Latinx) and mainly male (84.4%) and gay identified (62.2%). Nearly 20% of participants were 18-24 years old and 80% were ages 25-29. Participants who were 18-24 years old reported 2-3 times the odds for having worse sleep quality and mood and greater stress, anxiety, and weight gain compared with those 25-29 years old.ConclusionOur data provide a nuanced picture of the negative impacts that COVID-19 had on non-Latinx Black and Latinx young adults living with HIV in the U.S. Given that these adults represent a priority population for HIV treatment outcomes, it is critical to better understand the ongoing toll that these dual pandemics have on their lives.

IntroductionAlthough current antiretroviral therapy allows most people with HIV (PWH) to experience normal longevity with a good quality of life, an HIV cure remains elusive due to HIV reservoir formation within deep tissues. An HIV cure remains highly desirable to the community of PWH. This study reports on the perceived risks and benefits of participation in the Last Gift study, a study aimed at characterizing HIV reservoirs via post-mortem autopsy, among PWH at the end of life (EOL) and their next-of-kin (NOK)/loved ones.MethodsLast Gift participants (PWH with a terminal illness and/or near the end of life) and their NOK/loved ones were surveyed for perceptions of risks, benefits, and meaning for participation in the Last Gift study.ResultsThe average age of the 17 Last Gift participants was 66.6 years, 3 were females, 1 person identified as Hispanic, and 15 as Caucasian. The average age of the 17 NOK/loved ones was 56.7 years, and relationships to Last Gift participants included partner/spouse, sibling, friend, child, parent, grandparent, and nephew. The only perceived personal risk of the Last Gift among participants was the blood draws (3/17). NOK/loved ones perceived the following risks: blood draws (2/17), physical pain (3/17), worry that something bad will happen (2/17), and unpleasant side effects (1/17). Participants in Last Gift and NOK/loved ones indicated the study had various positive social effects. For both participants and NOK/loved ones, the most frequent perceived personal benefit of the Last Gift was the satisfaction of supporting HIV cure research.DiscussionParticipants perceived minimal personal and societal risks and valued the altruistic benefits of participating in the Last Gift study. Last Gift participants and NOK/loved ones were cautious about possible personal risks of EOL HIV cure research but still viewed that the emotional, psychological and societal benefits of participation outweighed potential risks.

The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL.Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit.We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations.

BackgroundOne of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it.MethodsWe conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable.ResultsAll four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants' comfort and needs at the EOL.ConclusionBecause of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research's impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings.

BackgroundInternet-based surveys are increasingly used for health research because they offer several advantages including greater geographic reach, increased participant anonymity, and reduced financial/time burden. However, there is also a need to address inherent challenges, such as the likelihood of fraudulent responses and greater difficulty in determining eligibility.MethodsWe conducted an online nationwide survey of 18-29 year olds living with HIV in the United States, to assess willingness to participate in HIV cure research. To ensure that respondents met age and HIV serostatus inclusion criteria, we instituted screening procedures to identify ineligible respondents using tools that were built into the survey platform (eg, reCAPTCHA, geolocation) and required documentation of age and serostatus before providing access to the incentivized study survey.ResultsOf 1308 eligibility surveys, 569 were incomplete or ineligible because of reported age or serostatus. Of the remaining 739 potentially eligible respondents, we determined that 413 were from fraudulent, bot, or ineligible respondents. We sent individual study survey links to 326 participants (25% of all eligibility survey respondents) whose eligibility was reviewed and confirmed by our study team.ConclusionOur multicomponent strategy was effective for identifying ineligible and fraudulent responses to our eligibility survey, allowing us to send the study survey link only to those whose eligibility we were able to confirm. Our findings suggest that proactive fraud prevention can be built into the screening phase of the study to prevent wasted resources related to data cleaning and unretrievable study incentives and ultimately improve the quality of data.

Youth and young adults living with HIV (YLWH) have a high HIV infection rate and suboptimal oral medication adherence. Biomedical researchers hope that long-acting antiretroviral therapy (LAART) modalities can help those who struggle with daily oral adherence. While adults living with HIV have expressed interest in LAART, little research has explored perspectives of YLWH. This study explores ART experiences and perspectives on LAART through qualitative interviews with twenty diverse YLWH (18-29) in the United States. Data were analyzed using framework analysis. Most participants were satisfied with their current ART yet had experienced side effects or had struggled with daily adherence. Preferences for improving daily oral ART included making pills smaller and reformulating ART into flavored chewable gummies. Most expressed enthusiasm for LAART, although needle aversion and previous injection drug use were potential barriers for some. Approximately half were interested in an ART patch, though its visibility and fear of stigmatization was concerning. Few expressed interest in implantable ART, calling it unappealing. Although younger people are most likely to benefit from these advancements in HIV treatment, additional research is needed to identify gaps in uptake and to further explore perspectives of YLWH to improve the success of new treatment modalities.

In the United States, young adults have the highest rates of new HIV infections, and are less likely to be aware of their infection, be engaged in care, or achieve HIV viral suppression. As biomedical HIV research increasingly focuses on achieving long-term suppression without antiretroviral therapy (ART) and finding an HIV cure, little is known about perceptions of young adults living with HIV (YLWH) regarding HIV cure research. We recruited a diverse sample of 20 YLWH (18-29 years old) to participate in individual semistructured qualitative interviews to explore knowledge and perceptions of HIV cure research, and motivations and barriers to participation. Most participants had little knowledge of HIV cure research. Motivators of HIV cure research participation included altruism, stigma reduction, and the elimination of the clinical burdens of HIV. Barriers included potential physical side effects, psychological distress, the possibility of disclosure as a result of participating, and the amount of time required to participate. Most participants had concerns about analytic treatment interruptions (i.e., ART interruption to assess HIV remission), and indicated that they would want more frequent laboratory testing and protection for their sex partners during this time. Finally, participants suggested that, if other YLWH are considering participation in cure research, they should first learn as much as possible about the research, and then consider the potential personal benefits and the contribution that they could make to science and their communities. As HIV cure research advances, the participation of YLWH will be critical. Our study provides knowledge about how YLWH view HIV cure research. More sociobehavioral research is needed to ensure that those who are most likely to be the decision-makers and beneficiaries of an HIV cure are included at all levels of research.

BackgroundThe pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.MethodsWe conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.DiscussionDespite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).ConclusionHIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.

BackgroundA unique window of opportunity currently exists to generate ethical and practical considerations presented by interventional HIV cure-related research at the end-of-life (EOL). Because participants would enroll in these studies for almost completely altruistic reasons, they are owed the highest ethical standards, safeguards, and protections. This qualitative empirical ethics study sought to identify ethical and practical considerations for interventional HIV cure-related research at the EOL.Methods and findingsWe conducted 20 in-depth interviews and three virtual focus groups (N = 36) with four key stakeholder groups in the United States: 1) bioethicists, 2) people with HIV, 3) HIV care providers, and 4) HIV cure researchers. This study produced six key themes to guide the ethical implementation of interventional HIV cure-related research at the EOL: 1) all stakeholder groups supported this research conditioned upon a clearly delineated respect for participant contribution and autonomy, participant understanding and comprehension of the risks associated with the specific intervention(s) to be tested, and broad community support for testing of the proposed intervention(s); 2) to ensure acceptable benefit-risk profiles, researchers should focus on limiting the risks of unintended effects and minimizing undue pain and suffering at the EOL; 3) only well-vetted interventions that are supported by solid pre-clinical data should be tested in the EOL translational research model; 4) the informed consent process must be robust and include process consent; 5) research protocols should be flexible and adopt a patient/participant centered approach to minimize burdens and ensure their overall comfort and safety; and 6) a participant's next-of-kin/loved ones should be a major focus of EOL research but only if the participant consents to such involvement.ConclusionsTo our knowledge, this empirical ethics study generated the first ethical and practical considerations for interventional HIV cure-related research at the EOL. The ethical complexities of such research must be considered now. We must navigate this ethical conundrum so that we are good stewards of the participants' extremely altruistic gifts by maximizing the impact and social value of this research. We hope that this study will serve as the foundation for future research and discussion on this topic.

BackgroundThe pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.MethodsWe conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.DiscussionDespite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).ConclusionHIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.