BackgroundHIV 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.MethodsTo 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.ResultsWe 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.ConclusionOur 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. (shrink)

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. (shrink)

BackgroundLiterature on issues relating to comprehension during the process of obtaining informed consent (IC) has largely focused on the challenges potential participants can face in understanding the IC documents, and the strategies used to enhance comprehension of those documents. In this review, we set out to describe the factors that have an impact on comprehension and the strategies used to enhance the IC process in sub-Saharan African countries.MethodsFrom November 2021 to January 2022, we conducted a literature search using a PRISMA (...) tool. We searched electronic databases (PubMed, EMBASE, EBSCOHOST) to identify relevant peer reviewed studies. We then reviewed the references of these articles to find additional literature that might have been missed through the initial search. We were particularly interested in full text articles in English that focused on the IC process in SSA published between 2006 and 2020. We included systematic reviews, and studies from Western and Asian countries that included data about SSA. We excluded articles that focused on medical interventions and studies that did not require IC.ResultsOut of the 50 studies included most were multi-country (n = 13) followed by single country studies in South Africa (n = 12); Kenya, Tanzania, Uganda (n = 5) each; Gambia, Ghana and Nigeria (n = 2)each ; and one each for Botswana, Malawi, Mali, Mozambique. We identified three areas of focus: (1) socio-cultural factors affecting IC; (2) gaps in the ethical and legal frameworks guiding the IC process; and (3) strategies used to improve participants’ understanding of IC.ConclusionOur review showed wide recognition that the process of achieving IC in SSA is inherently challenging, and there are limitations in the strategies aimed at improving comprehension in IC. We suggest that there is a need for greater flexibility and negotiation with communities to ensure that the approach to IC is suited to the diverse socio-cultural contexts. We propose moving beyond the literal translations and technical language to understanding IC comprehension from the participants’ perspectives and the researchers’ views, while examining contextual factors that impact the IC process. (shrink)

Consent processes for clinical trials involving HIV prevention research have generated considerable debate globally over the past three decades. HIV cure/eradication research is scientifically more complex and consequently, consent processes for clinical trials in this field are likely to pose a significant challenge. Given that research efforts are now moving toward HIV eradication, stakeholder engagement to inform appropriate ethics oversight of such research is timely. This study sought to establish the perspectives of a wide range of stakeholders in HIV treatment (...) and research to inform consent processes for cure research. In total, 68 South African stakeholders participated in two qualitative research modalities. In-depth interviews were conducted with a purposive sample of 42 individuals - audiotaped with consent. Twenty-six stakeholders participated in three focus group discussions. Thematic analysis of transcribed IDIs and FGDs was conducted. The majority of respondents indicated that there could be unique challenges in HIV cure research requiring special attention. In particular, given the complexity of cure science, translation of concepts into lay language would be critical for potential participants to adequately appreciate risks and benefits in early phase research with experimental interventions. Furthermore, to aid understanding of risks and benefits against a background of desperation for a cure, specially trained facilitators would be required to assist with a psychological assessment prior to consent to avoid curative misconceptions. Long-term participant engagement to assess durability of a cure would mean that the consent process would be prolonged, necessitating annual re-consent. Building trust to maintain such long-term relationships would be critical to retain study participants. Unique consent requirements for cure research in South Africa would include significant efforts to maximise understanding of trial procedures, risks and the need for long-term follow-up. However, the psychological dimension of cure must not be underestimated. Beyond an understanding of cure science, the emotional impact of HIV cure advances the discourse from cure to healing. Consequently, the consent process for cure research would need to be enhanced to include psychological support and counselling. This has several important implications for research ethics review requirements for consent in HIV cure research. (shrink)

BackgroundThe ethical concerns associated with HIV prevention and treatment research have been widely explored in South Africa over the past 3 decades. However, HIV cure research is relatively new to the region and significant ethical and social challenges are anticipated. There has been no published empirical enquiry in Africa into key informant perspectives on HIV cure research. Consequently, this study was conducted to gain preliminary data from South African HIV clinicians, researchers and activists.MethodsIn-depth interviews were conducted on a purposive sample (...) of fourteen key informants in South Africa. Audiotaped interviews were transcribed verbatim with concurrent thematic analysis. The perspectives of HIV clinicians, researchers and activists were captured. Analyst triangulation occurred as the data were analysed by three authors independently.ResultsThe rapid evolution of HIV cure research agendas was prominent with participants expressing some concern that the global North was driving the cure agenda. Participants described a symbiotic relationship between cure, treatment and prevention research necessitating collaboration. Assessing and managing knowledge and expectations around HIV cure research emerged as a central theme related to challenges to constructing ‘cure’ - how patients understand the idea of cure is important in explaining the complexity of cure research especially in the South African context where understanding of science is often challenging. Managing expectations and avoiding curative misconception will have implications for consent processes. Unique strategies in cure research could include treatment interruption, which has the potential to create therapeutic and ethical conflict and will be perceived as a significant risk. Ethical challenges in cure research will impact on informed consent and community engagement.ConclusionsIt was encouraging to note the desire for synergy amongst researchers and clinicians working in the fields of prevention, treatment and cure. Translation of complex HIV cure science into lay language is critical. Moving forward, RECs must be adequately constituted with scientific expertise and community representation when reviewing cure protocols. It is hoped that knowledge and resource sharing in the context of collaboration between research scientists working in cure and those working in treatment and prevention will accelerate progress towards cure. (shrink)

Trials with highly unfavourable risk–benefit ratios for participants, like HIV cure trials, raise questions about the quality of the consent of research participants. Why, it may be asked, would a person with HIV who is doing well on antiretroviral therapy be willing to jeopardise his health by enrolling in such a trial? We distinguish three concerns: first, how information is communicated to potential participants; second, participants’ motivations for enrolling in potentially high risk research with no prospect of direct benefit; and (...) third, participants’ understanding of the details of the trials in which they enrol. We argue that the communication concern is relevant to the validity of informed consent and the quality of decision making, that the motivation concern does not identify a genuine problem with either the validity of consent or the quality of decision making and that the understanding concern may not be relevant to the validity of consent but is relevant to the quality of decision making. In doing so, we derive guidance points for researchers recruiting and enrolling participants into their HIV cure trials, as well as the research ethics committees reviewing proposed studies. (shrink)