First-in-human HIV-remission studies: reducing and justifying risk

Dresser, Rebecca

doi:10.1136/medethics-2015-103115

Cited by 24 publications

(35 citation statements)

References 22 publications

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“…The aims of these studies are to obtain generalizable knowledge and identify novel approaches to cure disease [ 22 , 23 ]. EOL HIV cure-related research faces many of the same ethical challenges surrounding early-phase research, such as the need to ensure social value and scientific validity of the study, to carefully assess risks, and to ensure voluntary and informed consent [ 24 , 25 ]. In their seminal article ‘What makes clinical research ethical?’ [ 26 ], Emanuel and colleagues outlined seven requirements that provide a strong ethical foundation for clinical research.…”

Section: Ethical Principles For Clinical Research At the Eolmentioning

confidence: 99%

Ethical considerations for HIV cure-related research at the end of life

et al. 2018

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

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Section: Ethical Principles For Clinical Research At the Eolmentioning

confidence: 99%

Ethical considerations for HIV cure-related research at the end of life

et al. 2018

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“… 8–14 In such trials, participants are very likely to have no direct medical benefits and face uncertain and potentially high risks from the study intervention, invasive procedures and loss of therapeutic benefits from ART. 15 In the introduction to the special issue, Eyal argues that, at the very least, this is prima facie a ‘bad deal’ or ‘bad gamble’ for participants. Further, participants’ decisions to join may draw doubt on their rationality, generating a ‘risk/benefit ratio puzzle’ as to how anyone truly informed about cure trials could prudently choose to participate.…”

Section: Introductionmentioning

confidence: 99%

“… 7 Dresser also raises the important question of whether it is ethical for researchers to run such studies and for ethics boards to approve them because of their unfavourable risk/benefit ratio, and since participants seem likely to be worse off for participating. 15 …”

Section: Introductionmentioning

confidence: 99%

Ethics of treatment interruption trials in HIV cure research: addressing the conundrum of risk/benefit assessment

et al. 2017

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Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making study nested in a Thai acute HIV research cohort.In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks.These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach.

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“…An important aspect of conducting HIV cure research will involve communicating and framing expectations around earlyphase HIV cure experiments and scientific advances [5]. Stakeholders often overestimate the possibility of clinical benefits and underestimate the likelihood of risks in early-phase clinical research in general [22,23], and the same is true in earlyphase HIV cure research [6,[24][25][26]. While benefits of HIV cure research at this stage should be evaluated in terms of the production of incremental scientific knowledge [5], an increasing number of social sciences studies reveal that study participants in HIV cure research strongly value the benefits of inclusion (such as increased HIV knowledge or psychosocial benefits) [25,27].…”

Section: Behavioural and Social Sciences Researchmentioning

confidence: 99%

“…Examples of strategies under investigation include latent‐reversing agents, gene therapies, stem cell transplants, early ART, and immune‐based strategies, administered alone or in combination . It is well understood that initial HIV cure clinical studies will not lead to complete removal of the virus and will pose substantial risks to study participants . Some HIV cure clinical studies will require an intensively monitored ART pause (IMAP), also often referred to as analytical treatment interruption (ATI), to demonstrate efficacy of interventions .…”

Section: Introductionmentioning

confidence: 99%

Applying the Behavioural and Social Sciences Research (BSSR) Functional Framework to HIV Cure Research

et al. 2019

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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.

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First-in-human HIV-remission studies: reducing and justifying risk

Cited by 24 publications

References 22 publications

Ethical considerations for HIV cure-related research at the end of life

Ethical considerations for HIV cure-related research at the end of life

Ethics of treatment interruption trials in HIV cure research: addressing the conundrum of risk/benefit assessment

Applying the Behavioural and Social Sciences Research (BSSR) Functional Framework to HIV Cure Research

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