Participant experiences in a combination HIV cure-related trial with extended analytical treatment interruption in San Francisco, United States.

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.

"This Is Actually a Really Unique Moment in Time": Navigating Long-Acting HIV Treatment and HIV Cure Research with Analytical Treatment Interruptions-A Qualitative Interview Study in the United States.

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.

Participant experiences in HIV cure-directed trial with an extended analytical treatment interruption in Philadelphia, United States.

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.

To prescreen or not to prescreen for broadly neutralizing antibody sensitivity in HIV cure-related 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.

Increasing the meaningful involvement of women in HIV cure-related research: a qualitative interview study in the United States.

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.

'With this study, we have hope that something is coming': community members' perceptions of HIV cure-related research in Durban, South Africa - a qualitative focus group study.

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.

Perceived risks and benefits of enrolling people with HIV at the end of life in cure research in Southern California, United States.

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.

Community engagement group model in basic and biomedical research: lessons learned from the BEAT-HIV Delaney Collaboratory towards an HIV-1 cure.

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.

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.

A Community-Driven Framework to Prioritize the Use of Donated Human Biological Materials in the Context of HIV Cure-Related Research at the End of Life.

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.

Willingness of Racially Diverse Young Adults Living with HIV to Participate in HIV Cure Research: A Cross-Sectional Survey in the United States.

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.

"I Know That I Was a Part of Making a Difference": Participant Motivations for Joining a Cure-Directed HIV Trial with an Analytical Treatment Interruption.

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.

Participant experiences using novel home-based blood collection device for viral load testing in HIV cure trials with analytical treatment interruptions

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.

"It comes altogether as one:" perceptions of analytical treatment interruptions and partner protections among racial, ethnic, sex and gender diverse HIV serodifferent couples in the United States.

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.

Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States.

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.

"We are looking at the future right now": community acceptability of a home-based viral load test device in the context of HIV cure-related research with analytical treatment interruptions in the United States.

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.

Bringing social context into global biomedical HIV cure-related research: An urgent call to action.

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.

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States.

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

Short Communication: Population Representation in HIV Cure Research: A Review of Diversity Within HIV Cure Studies Based in the United States.

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.

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.

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).

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States.

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.