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

Abstract

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.

The Importance of Social Engagement in the Development of an HIV Cure: A Systematic Review of Stakeholder Perspectives

“…The perspectives of key populations (e.g., men who have sex with men, people who inject drugs, transgender people, next of kin, community members, and HIV activists) were most often considered when discussing ATI or end-of-life HIV cure research. Key populations accurately understood the meaning and importance of ATIs and end-of-life HIV cure research [ 22 , 53 , 70 , 71 ].…”

“…Across both qualitative and quantitative studies, these studies showed that professionals understand HIV cure clinical research, especially ATIs, as risky, with limited benefits, as some believed no direct health or indirect psychological benefits could be guaranteed [ 43 , 48 , 49 , 83 , 84 ]. The literature also showed that professionals often highlighted physical risks, such as side effects, HIV mutations, and HIV drug resistance, [ 32 , 43 , 48 , 56 , 59 , 66 , 70 , 80 , 81 , 83 – 86 ] and possible unknown risks [ 32 , 43 , 66 , 70 , 80 , 85 ]. Psychosocial risks, such as unrealistic trial expectations, negative impacts on participants’ social life and mental health, privacy concerns, and HIV transmission to sexual partners were also identified by professionals [ 32 , 43 , 56 , 59 , 66 , 70 , 81 , 84 , 86 ].…”

“…The literature also showed that professionals often highlighted physical risks, such as side effects, HIV mutations, and HIV drug resistance, [ 32 , 43 , 48 , 56 , 59 , 66 , 70 , 80 , 81 , 83 – 86 ] and possible unknown risks [ 32 , 43 , 66 , 70 , 80 , 85 ]. Psychosocial risks, such as unrealistic trial expectations, negative impacts on participants’ social life and mental health, privacy concerns, and HIV transmission to sexual partners were also identified by professionals [ 32 , 43 , 56 , 59 , 66 , 70 , 81 , 84 , 86 ].…”

“…These studies found that professionals identified several potential strategies to reduce known and unknown physical health risks. These included: only conducting the first-in-human studies with a strong scientific rationale, strict exclusion criteria for participants, and adequate monitoring of participants [ 62 , 70 , 86 , 87 ]. The qualitative studies on possible ATI risk reduction also provided suggestions as to how potential psychosocial risks might be limited.…”

“…The qualitative studies on possible ATI risk reduction also provided suggestions as to how potential psychosocial risks might be limited. Specifically, studies showed that professionals believed that community engagement in HIV cure research could prevent misconceptions and false hope [ 49 , 53 , 54 , 59 , 70 , 86 , 88 ]. Studies examining professional opinions on informed consent forms concluded that the term cure should be avoided in informed consent forms and that more effort should be made to improve vague and noninformative language about risks and benefits [ 49 , 86 , 89 ].…”