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Antiretroviral treatments successfully suppress and control HIV but cannot eliminate the virus. In recent years, much research has gone into developing a cure for HIV. This research comes with significant risks and limited clinical benefits to study participants. Little is known about the knowledge, willingness, motivations, and barriers of participating in HIV cure-related research. This is particularly true among young people living with HIV (YLWH), despite those

Summary Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures.

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 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.

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.

This viewpoint article critiques two recent articles examining ‘willingness to risk death’ to advance HIV cure-related research. The ‘willingness to risk death’ endpoint sends the wrong signal to the HIV cure-related research community about ongoing research in otherwise healthy volunteers living with HIV. Socio-behavioural scientists have examined the acceptability of a 99% risk of death scenario, which is unrealistic and would not be acceptable by current regulatory and ethical standards. We believe that the field needs robust and relevant socio-behavioural research reflecting ongoing biomedical HIV cure-related trials. These studies will need to withstand regulatory and ethical scrutiny if cure or remission regimens are to proceed to the licensing stage. The HIV cure-related research community must continue to protect the public trust in the HIV cure-related research field and sustain societal value generated by such research. We call for the utmost prudence in designing biomedical HIV cure trials as well as in setting up socio-behavioural research experiments related to these complex trials.

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.

The AIDS Clinical Trials Group (ACTG) A5345 study included an intensively monitored antiretroviral pause (IMAP), during which a cohort of participants temporarily stopped antiretroviral treatment during chronic HIV infection. We surveyed participant perceptions and understanding of A5345 using a cross-sectional sociobehavioral questionnaire. Participants completed the baseline questionnaire either before or after initiating the study's IMAP. Questionnaire responses were linked to existing demographic data. Quantitative responses were analyzed overall and stratified by IMAP status. Open-ended responses were analyzed using conventional content analysis. Thirty-two participants completed the baseline sociobehavioral questionnaire. Half (n = 16) completed it before (i.e., pre-IMAP initiation group) and half (n = 16) after IMAP initiation (i.e., post-IMAP initiation group). Eight pre-IMAP initiation respondents (50%) and 11 post-IMAP respondents (69%) responded “yes” when asked if they perceived any direct benefits from participating in A5345. Perceived societal-level benefits included furthering HIV cure-related research and helping the HIV community. Perceived personal-level benefits included the opportunity to learn about the body's response to IMAP and financial compensation. The majority of respondents—13 from each group (81% of each)—reported risks from participation, for example, viral load becoming detectable. A5345 participants perceived both societal- and personal-level benefits of study participation. While the majority of survey respondents perceived participatory risks, nearly one in five did not. Key messages pertaining to study-related risks and benefits may need to be clarified or reiterated periodically throughout follow-up in HIV cure-related studies with IMAPs. Clinical Trail Registration Number: NCT03001128.

Background Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms. Methods The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation. Results At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up. Conclusions Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

Given the dearth of regulatory guidance and empirical research on practices of providing payments to research participants, our study aimed to examine whether there were significant differences in payment amounts between sociobehavioral and biomedical studies and to examine study factors that may explain payment differences. This study reviewed 100 sociobehavioral and 31 biomedical protocols. Results showed that both biomedical studies and sociobehavioral studies had a wide variation of payments and, on average, the biomedical studies paid significantly more. Additionally, more biomedical studies offered payment than sociobehavioral studies. The primary factors that explained differences in payment amounts between sociobehavioral and biomedical studies were the number of study visits, study time, participation type, risk level, and research method. These findings provide pilot data to help inform future ethical decision-making and guidance regarding payment practices.

Long-acting injectable antiretroviral therapy (LAI-ART) is one of the latest advancements in HIV control with the potential to overcome oral ART barriers to adherence. The objective of this article is to anticipate and examine implementation considerations for LAI-ART using components of the PRISM model, a Practical, Robust Implementation and Sustainability Model for integrating research findings into practice. We conducted a scoping review from January to August 2020 of the growing literature on LAI-ART implementation and other fields using LAI therapies. Key considerations regarding LAI-ART were parsed from the searches and entered into the PRISM implementation science framework. The PRISM framework posed multiple questions for consideration in the development of an optimal implementation strategy for LAI-ART in the United States. These questions revealed the necessity for more data, including acceptability of LAI-ART among many different subgroups of people living with HIV (PLWH), cost effectiveness, patient satisfaction, and patient-reported outcomes, as well as more detailed information related to the external environment for optimal LAI-ART implementation. Ethical considerations of LAI-ART will also need to be considered. The anticipation of, and excitement for, LAI-ART represent the hope for a new direction for HIV treatment that reduces adherence barriers and improves prognoses for PLWH. We have a unique window of opportunity to anticipate implementation considerations for LAI-ART, so this new therapy can be used to its fullest potential. Outstanding questions remain, however, that need to be addressed to help achieve HIV suppression goals in diverse populations.

Author(s): Kanazawa, John; Gianella, Sara; Concha-Garcia, Susanna; Taylor, Jeff; Kaytes, Andy; Christensen, Christopher; Patel, Hursch; Ndukwe, Samuel; Rawlings, Stephen; Hendrickx, Steven; Little, Susan; Brown, Brandon; Smith, Davey; Dube, Karine | Abstract: 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.

HIV cure research carries serious risks and negligible benefits. We investigated how participants understand these risks and what influences their willingness to participate. Through internet-based and in-person convenience sampling, 86 HIV+ participants completed an experimental survey. Participants were randomized to read a standard consent form describing a hypothetical HIV cure study or one adapted using Fuzzy Trace Theory—a decision-making model to facilitate complex information processing. We measured consent understanding and cognitive (e.g., safe/harmful) and affective (e.g., concerning, satisfying) evaluations of HIV cure research. Participants who read the adapted consent form had improved consent understanding, but only positive affective evaluations were associated with a willingness to participate. Consent processes can use decision-making theories to facilitate comprehension of study information.

Some researchers continue to engage in “helicopter” or “parachute” research and do not ethically engage or collaborate with communities from which data are collected. This paper uses a case study to discuss the ethical issues arising from these research practices and the importance of increasing meaningful community involvement in research. Set in the context of research among older people living with HIV, the case study is followed by the perspectives of four research stakeholders. Through these perspectives, this paper demonstrates the ethical perils and harms that stem from research practices exemplified in the case. We argue instead for researchers to practice participatory research methods in line with community-based participatory research approaches (CBPR), good participatory practices (GPP), the Denver Principles, and CIOMS guidelines. Towards this end, we describe tools developed in collaboration with stakeholders in the research process to help researchers incorporate community participation and reduce unethical research conduct.

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.

Efforts to recognize and minimize the risk to study participants will be necessary to safely and ethically resume scientific research in the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. These efforts are uniquely challenging in the context of human immunodeficiency virus (HIV) cure clinical trials, which often involve complex experimental therapy regimens and perhaps analytic treatment interruption, in which participants pause antiretroviral therapy. In this viewpoint, we discuss our approach to reopening an HIV cure trial in this context, with a focus on key considerations regarding study design, informed consent and participant education, and study implementation. These recommendations might be informative to other groups seeking to resume HIV cure research in settings similar to ours.

Two HIV virologic control advances are in various stages of development, including long-acting antiretroviral therapy (ART) formulations and strategies aimed at sustained ART-free HIV control. Perceptions of risks and benefits toward HIV virologic control strategies may be different based on an individual's age due to differing experiences of the impacts of the domestic HIV epidemic, altruistic attitudes toward research participation, and general levels of engagement in health care. We examined preferences of HIV virologic control strategies by age groups. In 2018, we conducted a nationwide, online cross-sectional survey to examine differences in HIV virologic control strategies among a sample of people living with HIV who were

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.

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.

Purpose of review Partnerships between academia and the community led to historic advances in HIV and paved the way for ongoing community engagement in research. Three decades later, we review the state of community engagement in HIV research, discuss best practices as supported by literature, explore innovations, and identify ongoing gaps in knowledge. Recent findings The community of people living with and at risk for HIV remains actively involved in the performance of HIV research. However, the extent of participation is highly variable despite long standing and established principles and guidelines of good participatory practices (GPP) and community-based participatory research (CBPR). Current literature reveals that known barriers to successful community engagement continue to exist such as power differences, and poor scientific or cultural competency literacy. Several high-quality studies share their experiences overcoming these barriers and demonstrate the potential of CBPR through reporting of qualitative and quantitative outcomes. Summary Greater time and attention should be placed on the development of community engagement in HIV research. A large body of literature, including innovative cross-cutting approaches, exists to guide and inform best practices and mitigate common barriers. However, we recognize that true growth and expansion of CBPR within HIV and in other fields will require a greater breadth of research reporting qualitative and quantitative outcomes.

Introduction Little is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members’ perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research. Methods Two focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years. Results Qualitative focus group data revealed five major themes underlying study staff members’ multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants’ altruism, fulfillment, and control at the end of life, 2) perceptions of staff members’ close involvement in the Last Gift study, with sub-themes related to staff members’ cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites. Discussion Understanding staff members’ nuanced emotional and procedural experiences is crucial to the Last Gift study’s sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study’s potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.

Background The 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. Discussion As 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. Conclusion EOL 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.

Providing incentives is an accepted and common practice in human subjects research, including clinical HIV research. While we know that financial incentives among similar studies can greatly vary, surprisingly little research exists on how to determine when such incentives are excessive or constitute an "undue inducement." Multiple factors, such as risks and benefits, study procedures, study budget, historical precedent, recommendations from institutional review boards, advice from other investigators, and local regulations may influence decisions about appropriate incentives, but little empirical data exist about what incentives are offered to potential research participants. Rules for acceptable gifts, services, and compensation should consider study location and population, but without a clearer understanding of currently offered incentives and how these practices match up to ethical beliefs of appropriateness, we continue to follow perceived trends without critical assessment. Here, we present one potential approach to explore the impact of financial incentives on biomedical HIV research and to further clarify undue inducement: the development of a framework to support ethical decision-making about payment to participate. This framework is based on input from people living with HIV, biomedical HIV researchers, ethicists, former study participants, and IRB members and includes a database that allows for tracking payment practices.

Strategies to control HIV in the absence of antiretroviral therapy are needed to cure HIV. However, such strategies will require analytical treatment interruptions (ATIs) to determine their efficacy. We investigated how U.S. stakeholders involved in HIV cure research perceive ATIs. We conducted 36 in-depth interviews with three groups of stakeholders: 12 people living with HIV, 11 clinician-researchers, and 13 policy-makers/bioethicists. Qualitative data revealed several themes. First, there was little consensus on when ATIs would be ethically warranted. Second, the most frequent perceived hypothetical motivators for participating in research on ATIs were advancing science and contributing to society. Third, risks related to viral rebound were the most prevalent concerns related to ATIs. Stakeholders suggested ways to minimize the risks of ATIs in HIV cure research. Increased cooperation between scientists and local communities may be useful for minimizing risk. Further ethics research is necessary.

Introduction Participation in early-phase HIV cure studies includes clinical risks with little to no likelihood of clinical benefit. Examining the willingness of people living with HIV to participate is important to guide study design and informed consent. Our study examined the overall willingness of people living with HIV to participate in HIV cure research in the US, focusing on perceived risks and benefits of participation. Methods We undertook an online survey of adults living with HIV in the US. Survey questions were developed based on previous research and a scoping review of the literature. We quantitatively assessed individuals’ perceived risks and benefits of HIV cure-related research and respondents’ willingness to participate in different modalities of HIV cure studies. Results We recruited 409 study participants of whom 400 were eligible for the study and were included in the analysis (nine were not eligible due to self-declared HIV-negative status). We found >50% willingness to participate in 14 different types of HIV cure studies. Perceived clinical benefits and social benefits were important motivators, while personal clinical risks appeared to deter potential participation. Roughly two-thirds of survey respondents (68%) indicated that they were somewhat willing to stop treatment as part of HIV cure research. In the bivariate models, females, African Americans/blacks, Hispanics, individuals in the lowest income bracket, people living with HIV for longer periods of their lives, and people who were self-perceived ‘very healthy’ were less willing to participate in certain types of HIV cure studies than others. Multivariate results showed the perceived benefits (adjusted odds ratios >1) and perceived risks (adjusted odds ratios

Introduction The search for an HIV cure involves important behavioural and social processes that complement the domains of biomedicine. However, the field has yet to tap into the full potential of behavioural and social sciences research (BSSR). In this article, we apply Gaist and Stirratt’s BSSR Functional Framework to the field of HIV cure research. Discussion The BSSR Functional Framework describes four key research domains: (1) basic BSSR (understanding basic behavioural and social factors), (2) elemental BSSR (advancing behavioural and social interventions), (3) supportive BSSR (strengthening biomedically focused clinical trials), and (4) integrative BSSR (building multi‐disciplinary combination approaches for real‐world implementation). In revisiting and applying the BSSR Functional Framework, we clarify the importance of BSSR in HIV cure research by drawing attention to such things as: how language and communication affect the meaning of “cure” to people living with HIV (PLHIV) and broader communities; how cure affects the identity and social position of PLHIV; counselling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision‐making processes of potential study participants related to different cure strategies; HIV care providers’ perceptions and attitudes about their patients’ participation in cure research; potential social harms or adverse social events associated with cure research participation; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment. We also discuss the BSSR Functional Framework in the context of ATIs, which involve processes at the confluence of the BSSR domains. Conclusions To move HIV cure regimens through the translational research pathway, attention will need to be paid to both biomedical and socio‐behavioural elements. BSSR can contribute an improved understanding of the human and social dimensions related to HIV cure research and the eventual application of HIV cure regimens. The BSSR Functional Framework provides a way to identify advances, gaps and opportunities to craft an integrated, multi‐disciplinary approach at all stages of cure research to ensure the real‐world applicability of any strategy that shows promise.

Multiple strategies to cure HIV infection are under investigation, including cell and gene therapy (C&GT) approaches. Research, and ultimately treatment, with these novel strategies will require patients' willingness to participate. To elicit the perspectives of people living with HIV specific to these novel approaches, we conducted 4 focus group discussions with a diverse group of 19 English-speaking men and women living with HIV in care at a large academic HIV clinic in the northwestern United States. Thematic analysis indicated participants expressed initial fear about C&GT research. They articulated specific concerns about risks, including analytical treatment interruptions, and thought only a person in desperate straits would participate. They voiced significant mistrust of research in general and believed there was already a cure from HIV that was being withheld from the poor. Overall, they were satisfied with their health and quality of life on antiretroviral therapy. These findings suggest the importance of community engagement and educational efforts about C&GT for HIV cure to ensure optimal collaborative partnerships.

The literature on HIV therapeutics research is rife with terminology associating ���sterilisation��� with HIV cure. We find connotations of the word ���sterilising��� problematic for the HIV cure research field. In this viewpoint, we review associations of sterilising with concepts of disinfection or cleansing, as well as coerced sterilisation. We discuss emerging findings from socio-behavioural research that show aversion from people living with HIV towards the ���sterilising cure��� nomenclature. We call for more collaborations with people with HIV as partners to help define what would be a more acceptable terminology for describing an HIV cure.

Along with a dearth of regulatory guidance, little empirical research has examined factors related to participant payment in research. We conducted a cross-sectional study of 100 institutional review board (IRB)–approved sociobehavioral human subjects research protocols at a large research university in Southern California. The proportion of studies that paid participants differed significantly by type of research ( p < .001) and study population ( p = .009). The average payment amount also differed significantly by study population ( p < .001) and type of participation (in-person vs. remote; p < .001). In addition, studies that required more visits ( p < .001) and more time ( p = .011) paid significantly more than studies with fewer and shorter visits, respectively. These findings provide data to help inform future ethical payment practices.

Summary Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

Forty-four percent of Black transgender women are living with HIV, and many face challenges with HIV care engagement. An HIV cure has much to offer this population, however little HIV cure-related research has included them. We conducted 19 face-to-face in-depth interviews with 10 Black transgender women living with HIV. Interviews were audio recorded, transcribed verbatim, coded, and analyzed using content analysis. Our interview guide contained three categories: 1) perceptions of HIV cure-related research and participation, 2) perceptions of HIV treatment and treatment interruptions, and 3) considerations for transgender women and HIV cure-related research. Salient themes included skepticism about HIV cure strategies and limited benefits compared with an undetectable viral load. Willingness to interrupt HIV treatment for research was low and linked to being able to go back on the same HIV treatment without consequence when the study ended. Concerns about being a test subject and perceptions of risks versus benefits of various strategies also affected willingness to take part in HIV cure-related research. Centering the dignity and autonomy of research participants as well as building upon and supporting existing social networks were identified as important facilitators for engaging Black transgender women in HIV cure-related research. Specific to Black transgender women, other concerns included the desire for gender-affirming research staff, community-building among transgender women, and safety issues associated with risk of transphobic violence when traveling to study visits. Participants stressed the importance of HIV cure-related researchers providing accessible and complete information and expressing genuine care and concern for transgender communities.

We respond to Eyal et al.’s commentary focusing on how people living with HIV participating in HIV cure-related studies are defined. We argue that the types of participants enrolled in research cannot be dissociated from the study interventions, the types of anticipated risks, and the background standard of care. As the field of HIV cure research advances, more nuance and granularity will be needed to define research criteria and acceptable risk/benefit ratios for cure study participants, as well as specific tiered protocol designs that serve to protect various participant populations from untoward risks, especially in very early phase research with interventions known to have potentially serious toxicities. We highlight key lessons from the ACTIVATE study involving a latency-reversing agent, Panobinostat, for HIV cure study design involving “otherwise healthy volunteers”.

Over the past several years there has been intense activity directed at the possibility of achieving remission or eradication of HIV infection. Current assays for the measurement of latent HIV are insufficient to demonstrate complete clearance of replication-competent HIV. Therefore, the ultimate test for assessing whether investigational interventions have resulted in HIV remission or eradication is to interrupt standard antiretroviral therapy (ART) in a carefully controlled clinical trial setting. These procedures, known as analytic treatment interruptions (ATIs), raise important scientific and ethical questions. The lack of definitive assays for measuring viral reservoirs not only makes research on HIV remission or cure challenging, it also affects the ability to assess risks from ATIs themselves. In spite of these challenges, basic ethical criteria can be met with careful study design and close monitoring. In this brief report we outline ethical standards for HIV cure research involving ATIs. These criteria should be revisited as the science evolves.

Author(s): Dube, Karine; Perry, Kelly E; Mathur, Kushagra; Lo, Megan; Javadi, Sogol S; Patel, Hursch; Concha-Garcia, Susanna; Taylor, Jeff; Kaytes, Andy; Dee, Lynda; Campbell, Danielle; Kanazawa, John; Smith, David; Gianella, Sara; Auerbach, Judith D; Saberi, Parya; Sauceda, John A | Abstract: 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.

On May 30, 2018, the Right-To-Try bill, allowing the use of experimental, non-Food and Drug Administration (FDA)–approved drugs as a last resort for those unable to participate in clinical testing who have also exhausted all other treatment options, was signed into law ([1][1]). At the time this

In an essay, Karine Dubé and coauthors discuss the ethics of preclinical and clinical studies relevant to achieving an HIV cure.

Introduction Biomedical research towards an HIV cure is advancing in the United States and elsewhere, yet little is known about perceptions of risks and benefits among potential study participants and other stakeholders. We conducted a qualitative study to explore perceived risks and benefits of investigational HIV cure research among people living with HIV (PLWHIV), biomedical HIV cure researchers, policy-makers and bioethicists. Methods We conducted a qualitative research study using in-depth interviews with a purposive sample of PLWHIV, biomedical HIV cure researchers, policy-makers and bioethicists in 2015–2016. We analysed interview transcripts using thematic analysis anchored in grounded theory. Results We conducted and analyzed 36 key informant interviews. Qualitative analysis revealed four main findings. 1) Potential HIV cure study volunteers noted needing more information and education about the potential risks of HIV cure research. 2) Biomedical HIV cure researchers, policy-makers and bioethicists showed less awareness of social and financial risks of HIV cure research than PLWHIV. 3) Most respondents across the different categories of informants identified some risks that were too great to be acceptable in HIV cure research, although a subset of PLWHIV did not place an upper limit on acceptable risk. 4) PLWHIV showed a better awareness of potential psychological benefits of participating in HIV cure research than other groups of stakeholders. Conclusion Our research suggests that PLWHIV have a variable understanding of the individual risks, sometimes substantial, associated with participating in biomedical HIV cure research studies. Community engagement and increased research literacy may help improve community understanding. Intensive informed consent procedures will be necessary for ethical study implementation. The current state of HIV cure research offers greater potential benefits to society than to participants. There is likely to be disagreement among regulators, researchers, clinicians, and potential participants about what constitutes acceptable risk for HIV cure studies.

Early-phase HIV cure research is conducted against a background of highly effective antiretroviral therapy, and involves risky interventions in individuals who enjoy an almost normal life expectancy. To explore perceptions of three ethical topics in the context of HIV cure research—(a) equipoise, (b) risk–benefit ratios, and (c) “otherwise healthy volunteers”—we conducted 36 in-depth interviews (IDIs) with three groups of purposively selected key informants: clinician-researchers ( n = 11), policy-makers and bioethicists ( n = 13), and people living with HIV (PLWHIV; n = 12). Our analysis revealed variability in perceptions of equipoise. Second, most key informants believed there was no clear measure of risk–benefit ratios in HIV cure research, due in part to the complexity of weighing (sometimes unknown) risks to participants and (sometimes speculative) benefits to science and society. Third, most clinician-researchers and policy-makers/bioethicists viewed potential HIV cure study participants as “otherwise healthy volunteers,” but this perception was not shared among PLWHIV in our study.

In this issue of The Lancet HIV, Katherine Kranzer and colleagues report that economic incentives for caregivers in Zimbabwe increased uptake of HIV testing and counselling by children aged 8���17 years compared with caregivers with no financial incentive. HIV testing of groups that are hard to reach is a formidable challenge worldwide, and innovative strategies to reach adolescents in particular are crucial to reaching UNAIDS��� 90-90-90 goals

Among 149 men who survived Ebola virus disease (EVD) and donated semen 260–1016 days after EVD onset, Ebola virus (EBOV) ribonucleic acid (RNA) was detected in 13 (9%). Of 137 men who donated semen 2 years after EVD onset, 11 (8%) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, and it is unclear whether the detection of viral RNA represents the presence of infectious virus.

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multi-disciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.

Objectives To estimate the prevalence, incidence and determinants of herpes simplex type 2 (HSV-2) infection, and associations between HSV-2 and incident HIV infection, among women at higher risk for HIV infection in Beira, Mozambique. Methods Between 2009 and 2012, 411 women aged 18���35 years at higher risk of HIV acquisition (defined as having had two or more sexual partners in the month prior to study enrollment) were enrolled and followed monthly for one year. At each study visit, they were counseled, interviewed, and tested for HSV-2 and HIV antibodies. Results The HSV-2 prevalence at baseline was 60.6% (95% CI: 55.7% ���65.4%). Increasing age (aOR���=���2.94, 95% CI: 1.74���4.97, P

Background: Ebola virus (EBOV) RNA persistence in semen, reported sexual transmission, and sporadic clusters at the end of the 2013-2016 epidemic have prompted recommendations that male survivors refrain from unprotected sex unless their semen is confirmed to be EBOV free. However, there is no fully validated assay for EBOV detection in fluids other than blood. Methods: The Cepheid Xpert Ebola assay for EBOV RNA detection was validated for whole semen and blood using samples obtained from uninfected donors and spiked with inactivated EBOV. The validation procedure incorporated standards from Clinical and Laboratory Standards Institute and Good Clinical Laboratory Practices guidelines for evaluating molecular devices for use in infectious disease testing. Results: The assay produced limits of detection of 1000 copies/mL in semen and 275 copies/mL in blood. Limits of detection for both semen and blood increased with longer intervals between collection and testing, with acceptable results obtained up to 72 hours after specimen collection. Conclusions: The Cepheid Xpert Ebola assay is accurate and precise for detecting EBOV in whole semen. A validated assay for EBOV RNA detection in semen informs the care of male survivors of Ebola, as well as recommendations for public health.

Background The prevalence and determinants of HIV and late diagnosis of HIV in young women in Beira, Mozambique, were estimated in preparation for HIV prevention trials. Methods An HIV prevalence survey was conducted between December 2009 and October 2012 among 1,018 women aged 18���35 with two or more sexual partners in the last month. Participants were recruited in places thought by recruitment officers to be frequented by women at higher-risk, such as kiosks, markets, night schools, and bars. Women attended the research center and underwent a face-to-face interview, HIV counseling and testing, pregnancy testing, and blood sample collection. Results HIV prevalence was 32.6% (95% confidence interval (CI) 29.7%���35.5%). Factors associated with being HIV infected in the multivariable analysis were older age (p