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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.

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.

BackgroundCisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery.ObjectiveWe aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research.Materials and methodsWe conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data.ResultsWe recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality.ConclusionsOur empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

BACKGROUND: A feature of HIV cure trials is the need to interrupt treatment to test the efficacy of experimental interventions-a process known as analytical treatment interruptions (ATIs). OBJECTIVES: We report the experiences of participants after they completed an extended ATI. METHODS: From April to November 2022, we conducted post-ATI in-depth interviews with BEAT2 clinical trial (NCT03588715) participants who stopped ART while receiving an immunotherapy regimen. We used conventional content analysis to code the data. RESULTS: We conducted interviews with 11 Black/African American and three White/Caucasian participants (11 males, two females, and one transgender woman). The mean ATI was 38 weeks. Participants noted several significant experiences surrounding the interventions side effects, ATI, and returning to medication. Some participants had positive experiences with their ATI. Other participants were nervous during the ATI. Rising viral loads led some to feel a sense of failure. Although trial experiences were heterogeneous, participants unanimously had positive interactions with the clinical trial staff which facilitated their retention in the trial. Participants shared their experiences with the trial, including changes in expectations, experiences with experimental interventions and procedures, compensation as a measure of respect, effort, transportation, and effects of COVID-19 during the trial. Based on these results, we provide considerations for the conduct of future HIV cure-directed clinical trials involving ATIs. CONCLUSIONS: Managing expectations, focusing on participants contributions, and providing support to reduce feelings of having failed the research team and/or the HIV community following viral rebound should be part of HIV cure trial design. Discussing the mental health impact of rebound during consent, distinct from risk, is needed. Continued efforts to understand how people with HIV experience ATIs will improve future designs of HIV cure clinical trials.

The use of broadly neutralizing antibodies (bNAbs) as a cure-related research strategy for human immunodeficiency virus (HIV) has gained attention from the scientific community. bNAbs are specialized antibodies that target HIV-1 by binding to proteins on the surface of the virus, preventing the infection of human cells. In HIV-1 clinical studies assessing the use of bNAbs, it has been common practice to prescreen potential participants for bNAb sensitivity. However, the use of pre-screening in HIV-1 bNAb clinical trials is a topic of ongoing debate, with regard to its potential benefits and limitations. In this paper, we examine the possible benefits and limitations of pre-screening for bNAb sensitivity in HIV-1 cure-related studies, and suggest alternative methods which may be more effective or efficient at saving costs and time. Ultimately, the decision to use pre-screening in HIV-1 bNAb clinical trials should be based on a careful assessment of the potential benefits and limitations of this approach, as well as the specific needs, goals, design, and population of the study in question.

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.

BACKGROUND: Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in Durban, South Africa. OBJECTIVES: To explore community perspectives about HIV cure-related research. METHODS: Between July-August 2022, we conducted three focus groups with community members. We transcribed audio recordings verbatim and used content analysis to analyze the data. RESULTS: Twenty community members (13 women and 7 men) participated in three focus groups (HIV status not included). Participants viewed HIV cure-related research as a way to address the issue of defaulting on (not taking) HIV treatment. Participants expressed hesitancy around ATIs, since these contradict longstanding treatment adherence messages. Participants shared concerns around the risk of side effects from experimental interventions balanced against potential efficacy. They advocated for trial participants to have the right to decide whether to inform their sex partners about their HIV status and ATI participation, rather than research teams making disclosure mandatory. Focus group participants also emphasized the importance of using simple language to explain HIV cure-related research. CONCLUSIONS: With HIV cure trials set to launch across Africa in the future, there is a critical need to better understand and respond to local community needs and preferences and to adopt this as standard practice prior to regional trial implementation.

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.

Advancements in long-acting (LA) HIV treatment and cure research with analytical treatment interruptions (ATIs) have generated important scientific and implementation questions. There is an urgent need to examine challenges navigating the evolving HIV treatment and cure research landscape. From August to October 2022, we conducted 26 semistructured interviews with biomedical researchers and community members representing a predominantly woman demographic to explore the complexity of navigating the rapidly evolving HIV therapeutic and HIV cure research landscape. We purposively sampled individuals recruited from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories for HIV Cure Research. Audio files were transcribed verbatim and analyzed through a thematic approach, using an inductive and iterative process. Among 26 participants, 10 were biomedical researchers and 16 community members, including 11 were people with HIV. Three main themes emerged: (1) We are at a pivotal moment in the evolving landscape of HIV therapeutics and LA HIV treatment and HIV cure research should not be siloed but considered together; (2) There are challenges with engagement in HIV cure research and in switching between oral daily antiretroviral treatment and LA formulations and, mainly, the prolonged pharmacokinetic tail of these compounds matched with limited patient education about their impacts; and (3) There are unique opportunities as a result of this evolving therapeutic landscape, including the key role of decision support for people with HIV, centering around patient autonomy, and the need to learn from the lived experiences of people with HIV who choose LA treatment and/or participation in HIV cure research. Despite a bias toward the woman gender, our study identifies key considerations for navigating concurrent LA HIV treatment and HIV cure research with ATIs from both community members and biomedical researchers' perspectives. Achieving optimal HIV control remains a formidable challenge, necessitating robust interdisciplinary collaborations and engagement with key stakeholders. [ABSTRACT FROM AUTHOR]

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.

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.

BackgroundMost HIV cure-related studies involve interrupting antiretroviral treatment to assess the efficacy of pharmacologic interventions - also known as analytical treatment interruptions (ATIs). ATIs imply the risk of passing HIV to sexual partners due to the loss of undetectable HIV status. There has been a notable lack of attention paid to perceptions of ATIs among racial, ethnic, sex and gender minorities, and HIV serodifferent couples. These populations are among those most impacted by HIV in the United States. Future HIV cure research paradigms should equitably include considerations from these groups.MethodsFrom August - October 2020, we conducted in-depth interviews with 10 racial, ethnic, sex, and gender minority HIV serodifferent couples in geographically diverse regions of the United States to understand their perspectives about ATIs and partner protection measures to prevent secondary HIV transmissions because of participation in ATI studies. We used framework analysis to analyze the qualitative data.ResultsOf the 10 couples recruited, four identified as a gay couple, two as a gay and bisexual couple, two as a heterosexual couple, one as a gay and queer couple, and one as a queer couple. We found that HIV serodifferent couples in our study viewed ATIs as contradicting HIV treatment adherence messages. Couples expressed discomfort around ATIs in HIV cure research. They were concerned with the return of HIV detectability and worried ATIs might result in secondary HIV transmission. Participants were strongly in favor of using a range of partner protection measures during ATIs that included PrEP, HIV risk reduction counseling, and alternatives for penetrative sex practices. Couples also recommended that sex partners be consulted or involved as part of ATI trials.ConclusionsOur findings highlight new potential opportunities and strategies to mitigate risk of HIV transmission during ATIs among key groups historically under-represented in HIV cure research. Findings also underscore the relational aspects of ATI trials. We provide preliminary considerations for planning ATI trials with diverse HIV serodifferent partners. Future studies should continue to explore these issues among other types of partnerships, cultures, and socio-cultural settings.

Advances in science have ushered in a wave of new potential curative and control strategies for HIV that could eliminate the current requirement for life-long antiretroviral therapy (ART) for people living with HIV (PLWH). In this article, we argue that it is critical to consider social contexts in the development of HIV cure trial protocols. The biological and behavioral risk factors for HIV acquisition by study participants are inseparable from the social context in which these participants live. The article discusses an example of a cohort established to further HIV cure research that included social context, called the FRESH Acute HIV study, which combines a sociostructural intervention while conducting HIV prevention, treatment and cure-related research in Durban, South Africa. We make an urgent call to action to include sociobehavioral components as instrumental in future HIV cure trials in global context.

Despite disproportionate incidence and prevalence of HIV among transgender individuals, cisgender women, and racial and ethnic minority groups, all remain underrepresented in HIV cure research. As HIV cure trials are scaled up, there is emerging research on ways to mitigate risks of HIV acquisition for sexual partners of analytical treatment interruption (ATI) trial participants. As such, it is imperative that HIV cure researchers consider the implications of implementing ATIs in populations that are disproportionately affected by HIV, but largely underrepresented in trials to date. In this qualitative study, we sought to derive triangulated perspectives on the social and ethical implications regarding ATIs and partner protection strategies during ATIs among under-represented populations. We conducted 21 in-depth interviews with 5 types of informants: bioethicists, community members [people living with HIV (PLWH) and their advocates], biomedical HIV cure researchers, sociobehavioral scientists, and HIV care providers. We analyzed the data using conventional content analysis and reduced the data to important considerations for implementing ATI trials in diverse communities and settings. Our study revealed the following key themes: (1) attention must be paid to gender and power dynamics in ATI trials; (2) ATI trials should be designed and implemented through the lenses of intersectionality and equity frameworks; (3) ATI trials may have both positive and negative effects on stigma for PLWH and their partners; and (4) partnership dynamics should be considered when designing ATI protocols. Our study generated actionable considerations that could be implemented in ATI trials to promote their acceptability to communities that have been underrepresented in HIV cure research to date. Research teams must invest in robust community and stakeholder engagement to define best practices. Paying attention to representation and equity will also promote better and more equitable implementation of HIV cure strategies once these become ready for rollout.

BackgroundAn increasing number of HIV cure trials involve combining multiple potentially curative interventions. Until now, considerations for designing and implementing complex combination HIV cure trials have not been thoroughly considered.MethodsWe used a purposive method to select key informants for our study. Informants included biomedical HIV cure researchers, regulators, policy makers, bioethicists, and community members. We used in-depth interviews to generate ethical and practical considerations to guide the design and implementation of combination HIV cure research. We analyzed the qualitative data using conventional content analysis focused on inductive reasoning.ResultsWe interviewed 11 biomedical researchers, 4 community members, 2 regulators, 1 policy researcher, and 1 bioethicist. Informants generated considerations for designing and implementing combination interventions towards an HIV cure, focused on ethical aspects, as well as considerations to guide trial design, benefit/risk determinations, regulatory requirements, prioritization and sequencing and timing of interventions, among others. Informants also provided considerations related to combining specific HIV cure research modalities, such as broadly neutralizing antibodies (bNAbs), cell and gene modification products, latency-reversing agents and immune-based interventions. Finally, informants provided suggestions to ensure meaningful therapeutic improvements over standard antiretroviral therapy, overcome challenges of designing combination approaches, and engage communities around combination HIV cure research.ConclusionThe increasing number of combination HIV cure trials brings with them a host of ethical and practical challenges. We hope our paper will inform meaningful stakeholder dialogue around the use of combinatorial HIV cure research approaches. To protect the public trust in HIV cure research, considerations should be periodically revisited and updated with key stakeholder input as the science continues to advance.

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.

Abstract Introduction Achieving effective community engagement has been an objective of U.S. National Institutes of Health-funded HIV research efforts, including participation of persons with HIV. Community Advisory Boards (CABs) have remained the predominant model for community engagement since their creation in 1989. As HIV cure-directed research efforts have grown into larger academic-industry partnerships directing resources toward both basic and clinical research under the Martin Delaney Collaboratories (MDC), community input models have also evolved. The BEAT-HIV MDC Collaboratory, based at The Wistar Institute in Philadelphia, United States, implemented a three-part model for community engagement that has shown success in providing greater impact for community engagement across basic, biomedical, and social sciences research efforts. Discussion In this paper, we review the case study of the formation of the BEAT-HIV Community Engagement Group (CEG) model, starting with the historical partnership between The Wistar Institute as a basic research center and Philadelphia FIGHT as a not-for-profit community-based organization (CBO), and culminating with the growth of community engagement under the BEAT-HIV MDC. Second, we present the impact of a cooperative structure including a Community Advisory Board (CAB), CBO, and researchers through the BEAT-HIV CEG model, and highlight collaborative projects that demonstrate the potential strengths, challenges, and opportunities of this model. We also describe challenges and future opportunities for the use of the CEG model. Conclusions Our CEG model integrating a CBO, CAB and scientists could help move us towards the goal of effective, equitable and ethical engagement in HIV cure-directed research. In sharing our lessons learned, challenges and growing pains, we contribute to the science of community engagement into biomedical research efforts with an emphasis on HIV cure-directed research. Our documented experience with implementing the CEG supports greater discussion and independent implementation efforts for this model to engage communities into working teams in a way we find a meaningful, ethical, and sustainable model in support of basic, clinical/biomedical, social sciences and ethics research.

Background There 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). Objective To assess and understand experiences of people with HIV involved in a combination HIV cure-related trial with an extended ATI. Methods The 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. Results We 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. Conclusions Our 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.

Background Cisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery. Objective We aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research. Materials and methods We conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data. Results We recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality. Conclusions Our empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

Background A feature of HIV cure trials is the need to interrupt treatment to test the efficacy of experimental interventions—a process known as analytical treatment interruptions (ATIs). Objectives We report the experiences of participants after they completed an extended ATI. Methods From April to November 2022, we conducted post-ATI in-depth interviews with BEAT2 clinical trial (NCT03588715) participants who stopped ART while receiving an immunotherapy regimen. We used conventional content analysis to code the data. Results We conducted interviews with 11 Black/African American and three White/Caucasian participants (11 males, two females, and one transgender woman). The mean ATI was 38 weeks. Participants noted several significant experiences surrounding the interventions’ side effects, ATI, and returning to medication. Some participants had positive experiences with their ATI. Other participants were nervous during the ATI. Rising viral loads led some to feel a sense of failure. Although trial experiences were heterogeneous, participants unanimously had positive interactions with the clinical trial staff which facilitated their retention in the trial. Participants shared their experiences with the trial, including changes in expectations, experiences with experimental interventions and procedures, compensation as a measure of respect, effort, transportation, and effects of COVID-19 during the trial. Based on these results, we provide considerations for the conduct of future HIV cure-directed clinical trials involving ATIs. Conclusions Managing expectations, focusing on participants’ contributions, and providing support to reduce feelings of having failed the research team and/or the HIV community following viral rebound should be part of HIV cure trial design. Discussing the mental health impact of rebound during consent, distinct from risk, is needed. Continued efforts to understand how people with HIV experience ATIs will improve future designs of HIV cure clinical trials.

Background Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in Durban, South Africa. Objectives To explore community perspectives about HIV cure-related research. Methods Between July–August 2022, we conducted three focus groups with community members. We transcribed audio recordings verbatim and used content analysis to analyze the data. Results Twenty community members (13 women and 7 men) participated in three focus groups (HIV status not included). Participants viewed HIV cure-related research as a way to address the issue of defaulting on (not taking) HIV treatment. Participants expressed hesitancy around ATIs, since these contradict longstanding treatment adherence messages. Participants shared concerns around the risk of side effects from experimental interventions balanced against potential efficacy. They advocated for trial participants to have the right to decide whether to inform their sex partners about their HIV status and ATI participation, rather than research teams making disclosure mandatory. Focus group participants also emphasized the importance of using simple language to explain HIV cure-related research. Conclusions With HIV cure trials set to launch across Africa in the future, there is a critical need to better understand and respond to local community needs and preferences and to adopt this as standard practice prior to regional trial implementation.

BackgroundBackground: Analytical treatment interruptions (ATIs) in HIV cure-related research can result in trial participants becoming viremic with HIV, placing HIV-negative sexual partners at elevated risk of acquiring HIV.ObjectiveObjective:Our study aimed to generate ethical and practical considerations for designing and implementing appropriate risk mitigation strategies to reduce unintended HIV transmission events during ATIs.MethodsMethods: We conducted 21 in-depth interviews with five types of informants: bioethicists, community members, biomedical HIV cure researchers, socio-behavioral scientists/epidemiologists, and HIV care providers. We used conventional content analysis to analyze the data and generate considerations.ResultsResults: Key findings include: 1) Ethical permissibility of ATI trials depends on due diligence and informed consent to mitigate risks to participants and their sexual partners; 2) Participants should receive adequate support and/or counseling if they choose to disclose ATI participation to their partners; 3) Measures to protect sexual partners of trial participants from HIV transmission during ATIs should include referral to and/or provision of pre-exposure prophylaxis, as well as other available means of preventing HIV transmission; 4) There is uncertainty regarding the appropriate management of emerging sexually transmitted infections during ATI trials and possible protection measures for multiple and/or anonymous partners of ATI trial participants.ConclusionConclusion: While there is no way to completely eliminate the risk of HIV transmission to sexual partners during ATIs, HIV cure trialists and sponsors should consider the ethical concerns related to the sexual partners of ATI participants. Doing so is essential to ensuring the welfare of participants, their partners and the trustworthiness of research.

End-of-life (EOL) HIV cure-related research provides a novel approach to studying HIV reservoirs. The Last Gift is a rapid autopsy research study at the University of California San Diego that enrolls terminally ill people living with HIV (PLWHIV) with a desire to contribute to HIV cure-related research. We conducted in-depth baseline and follow-up interviews with Last Gift study participants. We analyzed interview data applying conventional content analysis. Since summer 2017, 13 participants have been enrolled (n = 11 males and 2 females; aged 45-89 years) and 8 participants interviewed. Terminal illnesses included cancers, heart diseases, and neurodegenerative illnesses. Our analysis revealed five key themes: (1) The Last Gift study has tremendous meaning for participants at the end of their life. (2) HIV-specific altruism was a primary motivator to join the Last Gift study, nested within the context of community, scientific advancement, and moral obligation. (3) Participants did not expect physical benefits yet they perceived emotional/psychological, financial, and societal/scientific benefits. (4) There were minimal participant-perceived risks and concerns. (5) Last Gift participants expressed immense gratitude toward study staff. The Last Gift study provides a framework for ethical HIV cure-related research at EOL and highlighted participants' perspectives, motivations, and experiences. Knowing how PLWHIV understand and experience such studies will remain critical to designing ethical, fully informed HIV cure research protocols that are acceptable to PLWHIV.

A growing number of people living with HIV/AIDS are participating in HIV cure-related research at the end of life (EOL). Due to the novelty of EOL HIV cure-related research, there is a need to understand how their next-of-kin (NOK) perceive such research. We conducted in-depth interviews with NOK of the Last Gift study participants at the University of California, San Diego. The Last Gift study occurs in the context of the EOL and involves a full body donation. NOK completed two interviews: (1) shortly after the participants' enrollment in the study and (2) following death. We applied thematic analysis to analyze qualitative data. NOK included seven individuals (five males and two females), including two spouses, one ex-partner, one sister, a grandmother/grandfather, and a close friend. Thematic analysis revealed five key themes: (1) NOK viewed the Last Gift program in a positive light and had an accurate overall understanding of the study; (2) NOK identified factors that motivated participants to donate their body to science; (3) NOK identified benefits of the Last Gift program for both the donors and themselves; (4) NOK did not perceive any physical risks or decisional regrets of study but wanted to minimize psychosocial impacts and ensure the dignity of participants at all times; and (5) NOK noted elements that remained essential to the successful implementation of EOL HIV cure-related research, such as early involvement and clear communication. Our study uniquely contributes to increased understanding and knowledge of what is important from the point of view of supportive NOK to ensure successful implementation of EOL HIV cure-related research. More research will be needed to understand perspectives of less supportive NOK.

A growing body of research is beginning to elucidate reasons people living with HIV (PLWHIV) might prefer oral daily antiretroviral treatment (ART) compared with emerging long-acting ART (LA-ART) or HIV remission strategies under investigation. Our objective is to provide qualitative insights into the reasons why PLWHIV might prefer one of these HIV control therapies over others. From May to August 2018, we implemented a semistructured cross-sectional survey of PLWHIV in the United States to better understand patient preferences around various HIV treatment and remission options. Using free text, respondents were asked to explain why they preferred one HIV control option over the other two. We analyzed responses to the open-ended survey questions on reasons for preferring oral daily ART versus LA-ART versus HIV remission strategies using conventional content analysis. The results showed that PLWHIV preferred oral daily ART because of its familiarity and known safety and efficacy profile, whereas those who preferred LA-ART would value the convenience it offers. Finally, HIV remission strategies would be preferred to avoid taking ART altogether. The qualitative results provide insights into reasons why PLWHIV in the United States might prefer oral daily ART versus novel therapies. More importantly, they provide information to better align HIV virological control strategies with end-user perspectives. To make informed choices around evolving HIV therapeutics, PLWHIV and HIV care providers would benefit from decision tools to better assess options and trade-offs. More research is needed on how best to effectively support PLWHIV and HIV care providers in shared decision-making.

For over a decade, the binary concepts of 'sterilizing' versus 'functional' cure have provided an organizing framework for the field of HIV cure-related research. In this article, we examine how the expression 'functional cure' is employed within the field, published literature, and community understanding of HIV cure research. In our synthesis of the different meanings attributed to 'functional cure' within contemporary biomedical discourse, we argue that employing the 'functional cure' terminology poses a series of problems. The expression itself is contradictory and inconsistently used across a wide array of HIV cure research initiatives. Further, the meaning and acceptability of 'functional cure' within communities of people living with and affected by HIV is highly variable. After drawing lessons from other fields, such as cancer and infectious hepatitis cure research, we summarize our considerations and propose alternative language that may more aptly describe the scientific objectives in question. We call for closer attention to language used to describe HIV cure-related research, and for continued, significant, and strategic engagement to ensure acceptable and more precise terminology.

IntroductionThe question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied.MethodsWe conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research-including the HIV prevention, treatment, and cure-related research fields.DiscussionAltruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism-either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research.ConclusionLessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.

There are two concurrent and novel major research pathways toward strategies for HIV control: (1) long-acting antiretroviral therapy (ART) formulations and (2) research aimed at conferring sustained ART-free HIV remission, considered a step toward an HIV cure. The importance of perspectives from people living with HIV on the development of new modalities is high, but data are lacking. We administered an online survey in which respondents selected their likelihood of participation or nonparticipation in HIV cure/remission research based on potential risks and perceived benefits of these new modalities. We also tested the correlation between perceptions of potential risks and benefits with preferences of virologic control strategies and/or responses to scenario choices, while controlling for respondent characteristics. Of the 282 eligible respondents, 42% would be willing to switch from oral daily ART to long-acting ART injectables or implantables taken at 6-month intervals, and 24% to a hypothetical ART-free remission strategy. We found statistically significant gender differences in perceptions of risk and preferences of HIV control strategies, and possible psychosocial factors that could mediate willingness to switch to novel HIV treatment or remission options. Our study yielded data on possible desirable product characteristics for future HIV treatment and remission options. Findings also revealed differences in motivations and preferences across gender and other sociodemographic characteristics that may be actionable as part of research recruitment efforts. The diversity of participant perspectives reveals the need to provide a variety of therapeutic options to people living with HIV and to acknowledge their diverse experiential expertise when developing novel HIV therapies.

Analytical treatment interruption (ATI), defined as a closely monitored clinical pause in antiretroviral therapy (ART), is a core component of many HIV cure-directed clinical studies. ATIs may cause significant physical and psychosocial risks for people living with HIV and, as a result, integrating participant and community perspectives into clinical trial designs that include an ATI is crucial to ensuring a successful and person-centered trial. We conducted semi-structured interviews with participants enrolling in the BEAT-2 cure-directed trial (NCT03588715). Interviews elicited participant motivations and decision-making processes for trial participation along with participants' perceptions of the ATI. Interviews were recorded, transcribed, and analyzed using a directed content analysis. Fourteen of 15 trial participants completed interviews. The majority were Black (79%) cisgender male (79%). Participants noted several significant motivating factors contributing to their desire to enroll in the HIV cure-directed clinical trial, the most prominent being a desire to find a cure for HIV and help others in the HIV community. HIV care teams were the most commonly identified resource for patients when making the decision to enroll in the trial, and family, friends, and romantic partners also played a significant role. Altruism was a primary motivation for participation, although participants also shared interest in learning about HIV science and research. Participants had a strong understanding of trial procedures and displayed significant trust in the study team to keep them informed and healthy during their participation. The ATI was a significant source of anxiety for participants. Their primary worry was that their prior antiretroviral therapy (ART) regimen would no longer be effective once they resumed ART. Despite these concerns, participants shared considerable excitement for continued participation in the trial and being a part of the search toward an HIV cure. [ABSTRACT FROM AUTHOR]

Introduction: Achieving effective community engagement has been an objective of U.S. National Institutes of Health-funded HIV research efforts, including participation of persons with HIV. Community Advisory Boards (CABs) have remained the predominant model for community engagement since their creation in 1989. As HIV cure-directed research efforts have grown into larger academic-industry partnerships directing resources toward both basic and clinical research under the Martin Delaney Collaboratories (MDC), community input models have also evolved. The BEAT-HIV MDC Collaboratory, based at The Wistar Institute in Philadelphia, United States, implemented a three-part model for community engagement that has shown success in providing greater impact for community engagement across basic, biomedical, and social sciences research efforts. Discussion: In this paper, we review the case study of the formation of the BEAT-HIV Community Engagement Group (CEG) model, starting with the historical partnership between The Wistar Institute as a basic research center and Philadelphia FIGHT as a not-for-profit community-based organization (CBO), and culminating with the growth of community engagement under the BEAT-HIV MDC. Second, we present the impact of a cooperative structure including a Community Advisory Board (CAB), CBO, and researchers through the BEAT-HIV CEG model, and highlight collaborative projects that demonstrate the potential strengths, challenges, and opportunities of this model. We also describe challenges and future opportunities for the use of the CEG model. Conclusions: Our CEG model integrating a CBO, CAB and scientists could help move us towards the goal of effective, equitable and ethical engagement in HIV cure-directed research. In sharing our lessons learned, challenges and growing pains, we contribute to the science of community engagement into biomedical research efforts with an emphasis on HIV cure-directed research. Our documented experience with implementing the CEG supports greater discussion and independent implementation efforts for this model to engage communities into working teams in a way we find a meaningful, ethical, and sustainable model in support of basic, clinical/biomedical, social sciences and ethics research. Plain English summary: HIV biomedical research groups have prioritized community support and representation as exemplified by the creation of Community Advisory Boards (CABs). Most CABs bring diverse stakeholders to advise on research objectives as part of their activities. The BEAT-HIV Delaney Collaboratory, based at The Wistar Institute in Philadelphia, is a research program created in 2016 to advance HIV cure research. To better engage communities beyond the CAB, the BEAT-HIV Delaney Collaboratory created a Community Engagement Group (CEG) model composed of three distinct components. First, the involvement of a community-based organization (CBO) introduces the historical know-how and relationship with the community. Philadelphia FIGHT fulfills the CBO role as a provider of primary care, education, advocacy, and research support for persons with HIV. Second, the BEAT-HIV CAB provides individual experiences and community input into HIV cure research and gives updates to the broader community about the status of research. Third, basic, clinical/biomedical, and social scientists implement the scientific goals of the BEAT-HIV Collaboratory. In this paper, we aimed to highlight the strengths, challenges, lessons learned, and opportunities of the BEAT-HIV CEG model. We also present examples of collaborative community engagement projects. Our paper contributes to the literature on novel community engagement approaches beyond the CAB. Based on our experience to date using the CEG, a multi-part community engagement model could help move us towards the goal of inclusive, effective, equitable, and ethical engagement in HIV cure research. [ABSTRACT FROM AUTHOR]

The use of broadly neutralizing antibodies (bNAbs) as a cure-related research strategy for human immunodeficiency virus (HIV) has gained attention from the scientific community. bNAbs are specialized antibodies that target HIV-1 by binding to proteins on the surface of the virus, preventing the infection of human cells. In HIV-1 clinical studies assessing the use of bNAbs, it has been common practice to prescreen potential participants for bNAb sensitivity. However, the use of pre-screening in HIV-1 bNAb clinical trials is a topic of ongoing debate, with regard to its potential benefits and limitations. In this paper, we examine the possible benefits and limitations of pre-screening for bNAb sensitivity in HIV-1 cure-related studies, and suggest alternative methods which may be more effective or efficient at saving costs and time. Ultimately, the decision to use pre-screening in HIV-1 bNAb clinical trials should be based on a careful assessment of the potential benefits and limitations of this approach, as well as the specific needs, goals, design, and population of the study in question.

Analytic treatment interruptions (ATIs) are currently the standard for assessing the impact of experimental interventions aimed at inducing sustained antiretroviral therapy (ART)-free remission in trials related to HIV cure. ATIs are associated with substantial risk to both study participants and their sexual partner(s). Two documented HIV transmissions occurring in the context of ATIs have been recently reported, but recommendations for mitigating the risk of such events during ATIs are limited. We outline a practical approach to risk mitigation during ATI studies and describe strategies we are utilising in an upcoming clinical trial that may be applicable to other centres.

Introduction: Although 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. Methods: Last 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. Results: The 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. Discussion: Participants 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.

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs. Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States. Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data. Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs. Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials.

Abstract Background Most HIV cure-related studies involve interrupting antiretroviral treatment to assess the efficacy of pharmacologic interventions – also known as analytical treatment interruptions (ATIs). ATIs imply the risk of passing HIV to sexual partners due to the loss of undetectable HIV status. There has been a notable lack of attention paid to perceptions of ATIs among racial, ethnic, sex and gender minorities, and HIV serodifferent couples. These populations are among those most impacted by HIV in the United States. Future HIV cure research paradigms should equitably include considerations from these groups. Methods From August – October 2020, we conducted in-depth interviews with 10 racial, ethnic, sex, and gender minority HIV serodifferent couples in geographically diverse regions of the United States to understand their perspectives about ATIs and partner protection measures to prevent secondary HIV transmissions because of participation in ATI studies. We used framework analysis to analyze the qualitative data. Results Of the 10 couples recruited, four identified as a gay couple, two as a gay and bisexual couple, two as a heterosexual couple, one as a gay and queer couple, and one as a queer couple. We found that HIV serodifferent couples in our study viewed ATIs as contradicting HIV treatment adherence messages. Couples expressed discomfort around ATIs in HIV cure research. They were concerned with the return of HIV detectability and worried ATIs might result in secondary HIV transmission. Participants were strongly in favor of using a range of partner protection measures during ATIs that included PrEP, HIV risk reduction counseling, and alternatives for penetrative sex practices. Couples also recommended that sex partners be consulted or involved as part of ATI trials. Conclusions Our findings highlight new potential opportunities and strategies to mitigate risk of HIV transmission during ATIs among key groups historically under-represented in HIV cure research. Findings also underscore the relational aspects of ATI trials. We provide preliminary considerations for planning ATI trials with diverse HIV serodifferent partners. Future studies should continue to explore these issues among other types of partnerships, cultures, and socio-cultural settings.

Abstract Background HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale. Methods To elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure. Results We interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions. Conclusion Our study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers.

Background People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome. Objective We assessed community acceptability of a novel home-based viral load test device. Methods In 2021, we conducted 15 interviews and 3 virtual focus groups with PWH involved in HIV cure research. We used conventional thematic analysis to analyze the data. Results PWH viewed the home-based viral load test device as a critical adjunct in ongoing HIV cure trials with ATIs. The ability to test for viral load at home on demand would alleviate anxiety around being off ART. Participants drew parallels with glucometers used for diabetes. A preference was expressed for the home-based test to clearly indicate whether one was detectable or undetectable for HIV to mitigate risk of HIV transmission to partners. Perceived advantages of the device included convenience, sense of control, and no puncturing of veins. Perceived concerns were possible physical marks, user errors and navigating the logistics of mailing samples to a laboratory and receiving test results. Participants expressed mixed effects on stigma, such as helping normalize HIV, but increased potential for inadvertent disclosure of HIV status or ATI participation. Increasing pluri-potency of the device beyond viral load testing (e.g., CD4+ count test) would increase its utility. Participants suggested pairing the device with telemedicine and mobile health technologies. Conclusions If proven effective, the home-based viral load test device will become a critical adjunct in HIV cure research and HIV care.

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.

BackgroundThe U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months.DiscussionAs end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders.ConclusionEOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs. Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States. Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data. Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs. Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials. [ABSTRACT FROM AUTHOR]

People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome. We assessed community acceptability of a novel home-based viral load test device. In 2021, we conducted 15 interviews and 3 virtual focus groups with PWH involved in HIV cure research. We used conventional thematic analysis to analyze the data. PWH viewed the home-based viral load test device as a critical adjunct in ongoing HIV cure trials with ATIs. The ability to test for viral load at home on demand would alleviate anxiety around being off ART. Participants drew parallels with glucometers used for diabetes. A preference was expressed for the home-based test to clearly indicate whether one was detectable or undetectable for HIV to mitigate risk of HIV transmission to partners. Perceived advantages of the device included convenience, sense of control, and no puncturing of veins. Perceived concerns were possible physical marks, user errors and navigating the logistics of mailing samples to a laboratory and receiving test results. Participants expressed mixed effects on stigma, such as helping normalize HIV, but increased potential for inadvertent disclosure of HIV status or ATI participation. Increasing pluri-potency of the device beyond viral load testing (e.g., CD4+ count test) would increase its utility. Participants suggested pairing the device with telemedicine and mobile health technologies. If proven effective, the home-based viral load test device will become a critical adjunct in HIV cure research and HIV care. [ABSTRACT FROM AUTHOR]

This mixed-methods study explored self-image among people with HIV participating in an HIV cure-related study involving analytical treatment interruptions (ATIs). Using both quantitative and qualitative approaches, we described how self-image emerged across study participation, focusing on internalized stigma, emotional strengths, and the psychosocial dimensions of study participation. Data come from the SCOPE-ATI substudy (NCT00187512) of the University of California San Francisco SCOPE cohort (NCT04359186). Quantitative data were collected at three timepoints: pre-ATI ( n = 15), post-ATI ( n = 12), and end of the study ( n = 14). We observed a general decline in self-image scores over time. However, participants maintained a moderately high agreement with statements about contributing to reducing HIV stigma through their involvement in the study. Qualitative interviews were collected pre-ATI ( n = 11), during ATI ( n = 8), and post-ATI ( n = 6). Qualitative findings revealed two major themes shaping self-image: (1) experiencing and reconciling internalized HIV stigma and (2) self-evaluations in relation to life purpose. Many participants expressed disappointment at having to resume antiretroviral therapy, viewing it as a reminder of their HIV status and its associated stigma. Nevertheless, some found purpose and pride in their participation, motivated by altruistic contributions to improving future HIV control options. The findings highlight the emotional complexities of participating in HIV cure research and underscore the need for psychosocial support throughout ATI studies. While most participants experienced a decline in self-image, some derived meaning and empowerment from their involvement. This study suggests that addressing emotional well-being and reinforcing participants' contributions to science can enhance their experience in future research.

Current trials toward an HIV cure involve combination strategies aimed at achieving durable antiretroviral treatment (ART)-free viral control or HIV elimination, many relying on analytical treatment interruptions (ATIs) to evaluate efficacy. Given the physical, psychosocial, and interpersonal risks associated with ATIs, it is critical to monitor participants' experiences so that support can be provided when needed. While qualitative approaches have been used in similar settings, we designed and implemented a series of short, closed-ended participant surveys in the University of California, San Francisco-amfAR trial, a single-arm multi-intervention HIV cure-related trial with an extended ATI. Surveys were administered at relevant trial timepoints to capture participants' ( n = 10) perspectives and experiences. These included their understanding of the trial, motivations, expectations, perceived risks, benefits, and burdens of trial participation, and their perspectives on restarting ART and partner protections. We describe these data using descriptive statistics and summarize lessons learned from implementing quantitative surveys in this complex trial. Our data indicate that all respondents understood the scientific goals and requirements of participating in the trial. Most were motivated to help advance research but many expressed anxiety about participating. During the trial, respondents had limited side effects, discomfort, and trial burnout. Those who completed surveys at ART restart reported mixed (positive and negative) feelings and challenges (e.g., missed doses) when restarting ART. Participants offered various methods for partner protection during ATIs and at ART restart. Many respondents expressed future willingness to participate in a similar HIV cure trial. While the number of respondents was small, these findings are consistent with concerns identified in guidance regarding these types of trials as well as qualitative findings from earlier studies. Moreover, we demonstrated that it is feasible to implement quantitative evaluations of participants' experiences. Such approaches should be implemented in future HIV cure trials to optimize human-centered research implementation.

Abstract Background We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. Methods PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. Results The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. Conclusions MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016)

Abstract Background One 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. Methods We 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. Results All 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. Conclusion Because 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.

Abstract Background An increasing number of HIV cure trials involve combining multiple potentially curative interventions. Until now, considerations for designing and implementing complex combination HIV cure trials have not been thoroughly considered. Methods We used a purposive method to select key informants for our study. Informants included biomedical HIV cure researchers, regulators, policy makers, bioethicists, and community members. We used in-depth interviews to generate ethical and practical considerations to guide the design and implementation of combination HIV cure research. We analyzed the qualitative data using conventional content analysis focused on inductive reasoning. Results We interviewed 11 biomedical researchers, 4 community members, 2 regulators, 1 policy researcher, and 1 bioethicist. Informants generated considerations for designing and implementing combination interventions towards an HIV cure, focused on ethical aspects, as well as considerations to guide trial design, benefit/risk determinations, regulatory requirements, prioritization and sequencing and timing of interventions, among others. Informants also provided considerations related to combining specific HIV cure research modalities, such as broadly neutralizing antibodies (bNAbs), cell and gene modification products, latency-reversing agents and immune-based interventions. Finally, informants provided suggestions to ensure meaningful therapeutic improvements over standard antiretroviral therapy, overcome challenges of designing combination approaches, and engage communities around combination HIV cure research. Conclusion The increasing number of combination HIV cure trials brings with them a host of ethical and practical challenges. We hope our paper will inform meaningful stakeholder dialogue around the use of combinatorial HIV cure research approaches. To protect the public trust in HIV cure research, considerations should be periodically revisited and updated with key stakeholder input as the science continues to advance.

Abstract Background The 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. Methods We 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. Discussion Despite 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). Conclusion HIV 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.

HIV is experienced across diverse populations, with gender and racial/ethnic minority populations bearing a significant proportion of disease. With National Institutes of Health (NIH) placing a priority on the enrollment of women and racial/ethnic minorities into studies, it is important to understand the diversity of participants in research. We sought to characterize how HIV cure research studies report data on diversity. A sampling frame of publications with funding provided by the Martin Delaney Collaboratories for HIV Research in 2019 was reviewed for reporting of demographic data. Of 55 publications that included research on humans/human specimens, only 51% provided any demographic description. There often is insufficient consideration of diversity of populations in HIV cure research. Ameliorating gaps in this regard will require recruitment of diverse populations/specimens and specifications to report demographic data in articles. This will ensure inclusion of diverse participants in HIV cure research from earliest laboratory to eventual phase III studies. [ABSTRACT FROM AUTHOR]

Background Background: Analytical treatment interruptions (ATIs) in HIV cure-related research can result in trial participants becoming viremic with HIV, placing HIV-negative sexual partners at elevated risk of acquiring HIV. Objective Objective:Our study aimed to generate ethical and practical considerations for designing and implementing appropriate risk mitigation strategies to reduce unintended HIV transmission events during ATIs. Methods Methods: We conducted 21 in-depth interviews with five types of informants: bioethicists, community members, biomedical HIV cure researchers, socio-behavioral scientists/epidemiologists, and HIV care providers. We used conventional content analysis to analyze the data and generate considerations. Results Results: Key findings include: 1) Ethical permissibility of ATI trials depends on due diligence and informed consent to mitigate risks to participants and their sexual partners; 2) Participants should receive adequate support and/or counseling if they choose to disclose ATI participation to their partners; 3) Measures to protect sexual partners of trial participants from HIV transmission during ATIs should include referral to and/or provision of pre-exposure prophylaxis, as well as other available means of preventing HIV transmission; 4) There is uncertainty regarding the appropriate management of emerging sexually transmitted infections during ATI trials and possible protection measures for multiple and/or anonymous partners of ATI trial participants. Conclusion Conclusion: While there is no way to completely eliminate the risk of HIV transmission to sexual partners during ATIs, HIV cure trialists and sponsors should consider the ethical concerns related to the sexual partners of ATI participants. Doing so is essential to ensuring the welfare of participants, their partners and the trustworthiness of research.