The HI V O pen Call on I nformed C onsent and E thics in Research (VOICE) for Adolescents and Young Adults: A Digital Crowdsourcing Open Call in Low- and Middle-Income Countries.

BACKGROUND: Many adolescents and young adults (AYAs; 10-24 years old) are excluded from HIV research because of social, ethical, and legal challenges with informed consent, resulting in limited AYA-focused data. We use a participatory approach to identify strategies for improving AYA consent processes in HIV research in low- and middle-income countries (LMICs). METHODS: We conducted a digital crowdsourcing open call for ideas to improve AYA consent to HIV research in LMICs. Crowdsourcing involves engaging a group of people in problem-solving, then sharing emergent solutions. Submissions were evaluated by 3 independent judges using predefined criteria, with exceptional strategies receiving prizes. Demographic data were collected, and textual data were qualitatively analyzed for emergent themes in barriers and facilitators for improving AYA consent in HIV research, guided by a socioecological model. RESULTS: We received 110 strategies total; 65 were eligible for evaluation, 25 of which were identified as finalists. Fifty-eight participants from 10 LMICs submitted the 65 eligible submissions, of which 30 (52%) were 18 to 24 years old. Thematic analysis identified 10 barriers to AYA consent, including HIV stigma, limited education, and legal/regulatory barriers. Strategies for improving AYA consent processes revealed 7 potential facilitators: enhancing AYA engagement in research, involving parents/guardians, improving education/awareness, improving institutional practices/policy, making research participation more AYA-friendly, enhancing engagement of other key communities of interest, and empowering AYA. CONCLUSIONS: Diverse communities of interest in LMICs developed compelling strategies to enhance informed consent that may improve AYA inclusion in HIV research. These data will be used to develop practical guidance on improving AYA consent processes.

Assessment of Consent Comprehension Among Kenyan Adolescents, Young Adults, and Parents: Comparison of Enhanced and Standard Consenting Procedures.

PURPOSE: Youth aged 15-19 years and parents of minors aged 15-17 years in sub-Saharan Africa are under-represented in empirical consent research. Thus, knowledge is limited concerning the adequacy of consent procedures and need for strategies to improve consent comprehension among these groups. We assessed comprehension following standard consent procedures and evaluated an enhanced procedure among Kenyan youth and parents. METHODS: Participants were adolescents aged 15-17 years (n = 273), their parents (n = 196), and young adults aged 18-19 years (n = 196). We used a quasi-experimental cohort design to implement standard and enhanced (single condition: extended discussion, test/feedback) consent procedures. Participants completed a 21-item informed consent comprehension assessment instrument. RESULTS: After standard consent procedures, mean comprehension scores were 11.36, 13.64, and 13.43 (score range: 0-21) among adolescents, young adults, and parents, respectively. About 6.2% of adolescents, 19.6% of young adults, and 21.4% of parents answered ≥ 80% of the questions correctly. After the enhanced procedures, comprehension scores (15.87 adolescents, 17.81 young adults, and 16.77 parents) and proportions answering ≥ 80% of the questions correctly (44.9% adolescents, 76.8% young adults, and 64.3% parents) increased significantly. Regression analysis indicated statistically significant differences (p < .001) in comprehension scores between the enhanced and standard groups (ß = 3.87 adolescents, ß = 4.03 young adults, and ß = 3.60 parents) after controlling for sociodemographic factors. DISCUSSION: Enhancing consent procedures with extended discussions, quizzes, and additional explanation where understanding is inadequate is a promising approach for improving comprehension. However, poorer comprehension among adolescents compared to young adults and parents underscores the need for research to identify additional approaches to improve understanding.

Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996.

The Essential Need for Trust When Transmission Risk Cannot Be Eliminated in HIV-Remission Trials.

Analytic treatment interruption (ATI) is scientifically necessary in HIV-remission ("cure") studies to test the effects of new interventions. However, stopping antiretroviral treatment poses risks to research participants and their sexual partners. Ethical debate about whether and how to conduct such studies has largely centered on designing risk-mitigation strategies and identifying the responsibilities of research stakeholders. In this paper, we argue that because the possibility of HIV transmission from research participants to partners during ATI cannot practicably be eliminated-that is, it is ineliminable-the successful conduct of such trials ultimately depends on relationships of trust and trustworthiness. We describe our experiences with conducting and studying HIV-remission trials with ATI in Thailand to examine the strengths, complexities, and limitations of the risk-mitigation and responsibility approaches and to explore ways in which the building of trust-and trustworthiness-may help enhance the scientific, practical, and ethical dimensions of these trials.

Ethical research when abortion access is legally restricted.

Risks and benefits of some clinical research may be altered.

Reporting Individual-Level Research Results from Neurocognitive and Psychological Research in People Living with HIV: Lessons from Dementia Research.

PURPOSE OF REVIEW: There are growing expectations for the return of individual-level research results (RoR), which promotes autonomy and potential clinical and personal benefits. There are ethical and practical challenges, however, that may be exacerbated in research that assesses neurocognitive and psychological outcomes, including HIV-associated neurocognitive disorder (HAND). This paper reviews central concepts for RoR and recent empirical and conceptual articles from Alzheimer's disorder (AD) as a model for HIV. RECENT FINDINGS: Data from AD studies indicate high participant interest and low risk of harm from RoR, though additional research is needed. Investigators report a range of benefits, potential risks, and feasibility concerns. Standardized, evidence-based approaches are needed for RoR. For HIV research, we recommend a default position of offering RoR for cognitive and psychological outcomes. Investigators should justify decisions not to return results after assessing the potential value and feasibility of RoR. Longitudinal research is needed for feasible and evidence-based best practices.

Corrigendum to 'Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok,' [Contemporary Clinical Trials Communication (2023)101054].

[This corrects the article DOI: 10.1016/j.conctc.2022.101054.].

Key ethical issues encountered during COVID-19 research: a thematic analysis of perspectives from South African research ethics committees.

BACKGROUND: The COVID-19 pandemic presents significant challenges to research ethics committees (RECs) in balancing urgency of review of COVID-19 research with careful consideration of risks and benefits. In the African context, RECs are further challenged by historical mistrust of research and potential impacts on COVID-19 related research participation, as well as the need to facilitate equitable access to effective treatments or vaccines for COVID-19. In South Africa, an absent National Health Research Ethics Council (NHREC) also left RECs without national guidance for a significant duration of the COVID-19 pandemic. We conducted a qualitative descriptive study that explored the perspectives and experiences of RECs regarding the ethical challenges of COVID-19 research in South Africa. METHODS: We conducted in-depth interviews with 21 REC chairpersons or members from seven RECs at large academic health institutions across South Africa that were actively involved in the review of COVID-19 related research from January to April 2021. In-depth interviews were conducted remotely via Zoom. Interviews (60-125 min) were conducted in English using an in-depth interview guide, until data saturation was achieved. Audio-recordings were transcribed verbatim and field notes were converted into data documents. Line-by-line coding of transcripts was performed, and data were organised into themes and sub-themes. An inductive approach to thematic analysis was used to analyse data. RESULTS: Five main themes were identified, namely: rapidly evolving research ethics landscape, extreme vulnerability of research participants, unique challenges to informed consent, challenges to community engagement during COVID-19, and overlapping research ethics and public health equity issues. Sub-themes were identified for each main theme. CONCLUSIONS: Numerous, significant ethical complexities and challenges were identified by South African REC members in the review of COVID-19 related research. While RECs are resilient and adaptable, reviewer and REC member fatigue were major concerns. The numerous ethical issues identified also highlight the need for research ethics teaching and training, especially in informed consent, as well as the urgent requirement for the development of national guidelines for research ethics during public health emergencies. Further, comparative analysis between different countries is needed to develop the discourse around African RECs and COVID-19 research ethics issues.

Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok.

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens. Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation. 406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0-6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined. There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators.

Stakeholder views on informed consent models for future use of biological samples in Malawi and South Africa.

BACKGROUND: Current advances in biomedical research have introduced new ethical challenges in obtaining informed consent in low and middle-income settings. For example, there are controversies about the use of broad consent in the collection of biological samples for use in future biomedical research. However, few studies have explored preferred informed consent models for future use of biological samples in Malawi and South Africa. Therefore, we conducted an empirical study to understand preferred consent models among key stakeholders in biomedical studies that involve collection of biological samples in Malawi and South Africa. The main objective of the study was to explore views of key stakeholders on current policies on informed consent in Malawi and South Africa. METHODS: This was a qualitative study involving in-depth interviews and focus group discussions. Thirty-four in-depth interviews and 6 focus group discussions were conducted with REC members, Funders, Policymakers, CAB members and Research Participants in Malawi and South Africa to gather their views on models of informed consent. The study was conducted in Cape Town, South Africa, and Blantyre and Lilongwe in Malawi. RESULTS: Most key stakeholders preferred broad consent and tiered consent to specific consent. Some participants expressed a strong preference for specific consent to other models of informed consent in biomedical research. Few participants did not have any preference for a consent model, opting for any consent model which provides adequate information about the proposed research and what their national consent regulations require. Finally, very few participants preferred blanket consent to other informed consent models. CONCLUSIONS: This study aimed to help fill the gap in the scientific literature on key stakeholder views on consent models for future use of biological samples in Malawi and South Africa. The findings of the study have provided some evidence that may support policies on permissible consent models for future use of biological samples in sub-Saharan Africa considering the differences in informed consent regulations and guidelines. Finally, the findings can inform ongoing discussions on permissible consent models to be used for future use of biological samples.

A review of public health, social and ethical implications of voluntary medical male circumcision programs for HIV prevention in sub-Saharan Africa.

Ideally, the benefits of public health interventions should outweigh any associated harms, burdens, and adverse unintended consequences. The intended benefit of voluntary medical male circumcision (VMMC) programs in eastern and southern Africa (ESA) is the reduction of HIV infections. We review the literature for evidence of reductions in HIV incidence, evaluate the extent to which decreases in HIV incidence can be reasonably attributed to VMMC programs, and summarize social harms and ethical concerns associated with these programs. Review findings suggest that HIV incidence had been declining across ESA since before the large-scale rollout of VMMC as a public health intervention, and that this decline may be due to the combined effects of HIV prevention and treatment interventions, such as expanded antiretroviral therapy. The independent effect of VMMC programs in reducing HIV infections at the population level remains unknown. On the other hand, VMMC-associated evidence is increasing for the existence of negative social impacts such as stigmatization and/or discrimination, and ethically problematic practices, including lack of informed consent. We conclude that the relationship between the benefits and burdens of VMMC programs may be more unfavorable than what has been commonly suggested by proponents of global VMMC campaigns.

Ethics and regulatory complexities posed by a pragmatic clinical trial: a case study from Lilongwe, Malawi.

Background: Pragmatic clinical trials generally rely on real world data and have the potential to generate real world evidence. This approach arose from concerns that many trial results did not adequately inform real world practice. However, maintaining the real world setting during the conduct of a trial and ensuring adequate protection for research participants can be challenging. Best practices in research oversight for pragmatic clinical trials are nascent and underdeveloped, especially in developing countries. Methods: We use the PRECIS-2 tool to present a case study from Lilongwe in Malawi to describe ethical and regulatory challenges encountered during the conduct of a pragmatic trial and suggest possible solutions. Results: In this article, we highlight the following six issues: (1) one public facility hosting several pragmatic trials within the same period; (2) research participants refusing financial incentives; (3) inadequate infrastructure and high workload to conduct research; (4) silos among partner organisations involved in delivery of health care; (5) individuals influencing the implementation of revised national guidelines; (6) difficulties with access to electronic medical records. Conclusion: Multiple stakeholder engagement is critical to the conduct of pragmatic trials, and even with careful stakeholder engagement, continuous monitoring by gatekeepers is essential. In the Malawian context, active engagement of the district research committees can complement the work of the research ethics committees (RECs).

Perceptions of HIV cure and willingness to participate in HIV cure-related trials among people enrolled in the Netherlands cohort study on acute HIV infection.

Background: People who initiate antiretroviral therapy (ART) during acute HIV infection are potential candidates for HIV cure-related clinical trials, as early ART reduces the size of the HIV reservoir. These trials, which may include ART interruption (ATI), might involve potential risks. We explored knowledge and perception of HIV cure and willingness to participate in cure-related trials among participants of the Netherlands Cohort Study on Acute HIV infection (NOVA study), who started antiretroviral therapy immediately after diagnosis of acute HIV infection. Methods: We conducted 20 in-depth qualitative interviews with NOVA study participants between October-December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Findings: Most participants had limited knowledge of HIV cure and understood HIV cure as complete eradication of HIV from their bodies. HIV cure was considered important to most participants, mostly due to the stigma surrounding HIV. More than half would consider undergoing brief ATI during trial participation, but only one person considered extended ATI. Viral rebound and increased infectiousness during ATI were perceived as large concerns. Participants remained hopeful of being cured during trial participation, even though they were informed that no personal medical benefit was to be expected. Interpretation: Our results highlight the need for thorough informed consent procedures with assessment of comprehension and exploration of personal motives prior to enrollment in cure-related trials. Researchers might need to moderate their expectations about how many participants will enroll in a trial with extended ATI.

Advancing a Data Justice Framework for Public Health Surveillance.

BACKGROUND: Bioethical debates about privacy, big data, and public health surveillance have not sufficiently engaged the perspectives of those being surveilled. The data justice framework suggests that big data applications have the potential to create disproportionate harm for socially marginalized groups. Using examples from our research on HIV surveillance for individuals incarcerated in jails, we analyze ethical issues in deploying big data in public health surveillance. METHODS: We conducted qualitative, semi-structured interviews with 24 people living with HIV who had been previously incarcerated in county jails about their perspectives on and experiences with HIV surveillance, as part of a larger study to characterize ethical considerations in leveraging big data techniques to enhance continuity of care for incarcerated people living with HIV. RESULTS: Most participants expressed support for the state health department tracking HIV testing results and viral load data. Several viewed HIV surveillance as a violation of privacy, and several had actively avoided contact from state public health outreach workers. Participants were most likely to express reservations about surveillance when they viewed the state's motives as self-interested. Perspectives highlight the mistrust that structurally vulnerable people may have in the state's capacity to act as an agent of welfare. Findings suggest that adopting a nuanced, context-sensitive view on surveillance is essential. CONCLUSIONS: Establishing trustworthiness through interpersonal interactions with public health personnel is important to reversing historical legacies of harm to racial minorities and structurally vulnerable groups. Empowering stakeholders to participate in the design and implementation of data infrastructure and governance is critical for advancing a data justice agenda, and can offset privacy concerns. The next steps in advancing the data justice framework in public health surveillance will be to innovate ways to represent the voices of structurally vulnerable groups in the design and governance of big data initiatives.

Does Venue of HIV Testing and Results Disclosure in the Context of a Research Study Affect Adolescent Health and Behavior? Results from a Study in Western Kenya.

Ethical concerns about risks to minor adolescents participating in HIV prevention research is a barrier to their inclusion. One concern is whether HIV testing and results disclosure venue affects the health and behavior of adolescent participants. We assessed for differential effects on quality of life (QOL), depressive symptoms, and sexual behavior due to (1) testing venue (home or health facility) and (2) test result (HIV-positive, HIV-negative, indeterminate). We collected data at three timepoints (baseline, 2-month follow-up, 12-month follow-up) from 113 Kenyan adolescents aged 15-19 (51% female). We analyzed the data using linear mixed effects models for the QOL and depressive symptoms outcomes and a logistic model for the sexual behavior outcome. Results showed a small mental health benefit for adolescents tested for HIV at a health facility compared with home. There was little evidence that testing venue influenced sexual behavior or that test results moderated the effects of HIV testing across all outcomes. The decision to conduct HIV testing at home or a health facility may not be very consequential for adolescents' health and behavior. Findings underscore the need to critically examine assumptions about adolescent vulnerability to better promote responsible conduct of HIV prevention research with youth in sub-Saharan Africa.

Attitudes About Analytic Treatment Interruption (ATI) in HIV Remission Trials with Different Antiretroviral Therapy (ART) Resumption Criteria.

HIV remission trials often require temporary stopping of antiretroviral therapy (ART)-an approach called analytic treatment interruption (ATI). Trial designs resulting in viremia raise risks for participants and sexual partners. We conducted a survey on attitudes about remission trials, comparing ART resumption criteria (lower-risk "time to rebound" and higher-risk "sustained viremia") among participants from an acute HIV cohort in Thailand. Analyses included Wilcoxon-Ranks and multivariate logistic analysis. Most of 408 respondents supported ATI trials, with slightly higher approval of, and willingness to participate in, trials using time to rebound versus sustained viremia criteria. Less than half of respondents anticipated disclosing trial participation to partners and over half indicated uncertainty or unwillingness about whether partners would be willing to use PrEP. Willingness to participate was higher among those who rated higher trial approval, lower anticipated burden, and those expecting to make the decision independently. Our findings support acceptability of ATI trials among most respondents. Participant attitudes and anticipated behaviors, especially related to transmission risk, have implications for future trial design and informed consent.

Improving the Continuity of Care for People Living with HIV Experiencing Incarceration in North Carolina Jails: Stakeholder Perspectives.

BACKGROUND Jail detention can disrupt the continuity of care for people living with HIV/AIDS (PLWH). Using a state's "Data to Care" (D2C) program might help overcome this barrier, but raises important questions of data security, personal privacy, resource allocation, and logistics.METHODS As part of a study involving in-depth expert stakeholder interviews, a 1-day workshop was convened to identify and discuss potential ethical challenges in extending North Carolina's D2C program to jail settings. Workshop participants included public health officials, community advocates, HIV clinicians, jail administrators, privacy experts, criminal justice researchers, and a formerly incarcerated PLWH. Workshop participants discussed the results of earlier stakeholder interviews with the goal of identifying the most important points to consider in assessing the merits of extending D2C surveillance to jail settings.RESULTS Although the workshop participants expressed support for improving the continuity of HIV care for jail detainees, they had mixed perspectives on whether a jail-based D2C program should include in-jail or post-release follow-up interventions. Their positions were influenced by their views on 4 sets of implementation issues: privacy/data-sharing; government assistance/overreach; HIV criminalization/exceptionalism; and community engagement.LIMITATIONS The limitations of this stakeholder engagement exercise include its purposive recruitment, relatively small number of participants, and limited duration.CONCLUSIONS Improving the continuity of HIV care in particular jail settings will depend on a number of local considerations. In deciding between models featuring in-jail and post-release follow-up care, the most important of these considerations will be the possibility of establishing good partnerships between the jail, the health department, and the community. Additional research on the dynamics and impact of different models is needed.

Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection.

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection-the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval.