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

Abstract

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.

HIV Cure Research: Risks Patients Expressed Willingness to Accept

“…For example, one study performed in Thailand found that participants in HIV cure research were motivated by giving back to their community and by the potential benefits not only to themselves but also to the investigators and others with HIV. 7 Additional studies have found similar other-oriented motivations. 8 People's willingness to take risk for an HIV cure also goes beyond the clinical or health benefit, and the fact that people living with HIV are often quite healthy does not preclude the possibility that a cure would significantly improve their overall quality of life.…”

“…But the risk‐benefit ratio could depend on what people living with HIV value about seeking a cure. For example, one study performed in Thailand found that participants in HIV cure research were motivated by giving back to their community and by the potential benefits not only to themselves but also to the investigators and others with HIV 7 . Additional studies have found similar other‐oriented motivations 8 …”

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

“…Supportive BSSR also includes understanding how participants make decisions to participate in HIV cure research. With the support of biomedical HIV cure research teams, socio‐behavioural scientists are increasingly able to understand decision‐making processes of those who decide to participate (or not) in HIV cure research, rather than relying on hypothetical intentions and perceptions . Supportive BSSR may also include patient‐reported outcomes (PROs) and patient‐reported experience measures (PREMs) completed by participants to assess the effects of study participation on various critical domains, such as well‐being, symptoms, functioning, adverse events and experiences with interventions, studies and ATIs .…”

The Role of Inclusion Benefits in Ethics Committee Assessment of Research Studies

“…Our data revealed that many focus group participants had a profoundly positive conception of participation in health research, including studies conferring seemingly few personal benefits from the research team's perspective. 7 For example, some of these studies involved analytic treatment interruption, that is, cessation of antiretroviral treatment in order to test the effects of a cure or remission intervention. 5 Our findings were consistent with similar research in Kenya related to participant perceptions of benefit.…”

“…Our social science research on participant experiences in the trials, however, revealed a different story about personal benefit. 7 For example, some of these studies involved analytic treatment interruption, that is, cessation of antiretroviral treatment in order to test the effects of a cure or remission intervention. Since participants were doing well on treatment, analytic treatment interruption was identified by researchers and ethics committees as a significant medical risk.…”