Investigating Psychosocial Experiences of HIV Cure Trial Participants Undergoing Extended HIV Treatment Interruptions: Implications for Ethical Conduct

HIV cure research is a high-priority for the National Institutes of Health and is targeting a strategy that can lead to sustained antiretroviral treatment-free suppression. However, because there are no clear biomarkers for an HIV cure – unlike CD4+ count and viral load as markers of treatment efficacy – the only way to evaluate the efficacy of a strategy is to require otherwise healthy people living with HIV who have achieved viral suppression to pause their treatment. This pausing is called an analytical treatment interruption and is the most controversial aspect of HIV cure research. Further, to advance HIV cure research, participants are required to tolerate extended treatment interruptions, which are long periods of high levels of uncontrolled viremia. The goals of the proposed research are to investigate the informed consent process and participants’ understanding and experiences with extended treatment interruptions and use a robust consensus-building technique to resolve the most pressing ethical challenges in HIV cure research. Aims 1 – 2 are nested within four entirely unique trials in the United States with a combined total of 120 participants. Aim 1 will evaluate the quality of informed consent in 30 participants going through a treatment interruption study, and survey data will be collected measuring perceived benefits, risks, understanding of study procedures, expectations, and relevant psychological domains. Aim 2 will prospectively evaluate the psychological experiences, quantitatively and qualitatively, of HIV cure research participants before, during and after treatment interruptions. This involves the analysis of strategically placed, and fully integrated prospective psychological survey assessments and interviews from study entry to exit. Surveys include measures of anxiety-related outcomes to monitor potential for psychological harm and stress levels during the treatment interruption. Aim 3 involves the use of a hybrid Delphi process to build consensus for strategies to address evolving ethical challenges in HIV cure research. A panel of experts are selected from across the U.S. to engage in four rounds of surveys, with stakeholders providing input on survey results in between rounds. The goal is to arrive at consensus around how to promote engagement in HIV cure research among all populations with HIV in the United States, how to implement treatment interruptions safely, how to address psychological harms, and how to protect partners. The proposed aims will show how people living with HIV understand and experience cutting-edge HIV cure strategies. The potential impact of this research will result in concrete sets of recommendations and actionable items to enhance the informed consent process to reduce consent misunderstanding, report on any psychological harms and development of risk mitigation plans, and set guidance on implementation of HIV cure research moving forward