Abstract / Summary
Evaluation of the efficacy of immunotherapeutic strategies aimed at achieving durable antiretroviral treatment (ART)-free control within a clinical trial relies on analytical treatment interruptions (ATIs). ATIs involve stopping ART to assess post-intervention efficacy with frequent viral load monitoring. These trials rely on participant commitment but also involve uncertainty about the timing and experience of viral rebound, transmission risk, and impacts on personal and sexual relationships. Understanding participants' lived experiences is critical to participant involvement and retention and to designing ATI studies that are ethical, feasible, and acceptable.
We conducted a qualitative study involving semi-structured interviews with 20 cisgender men living with HIV enroled in the phase 2 double-blinded randomised placebo-controlled RIO trial of HIV-specific broadly neutralising antibodies between January and May 2025 in the United Kingdom. We transcribed, coded and analysed the interviews using thematic analysis.
The participants described being motivated by scientific altruism but had worries about stopping ART. During the ATI, participants found breaking their daily pill-taking routine challenging, yet a majority described feelings of liberation thereafter. The participants preferred once weekly viral load testing, as it reassured safety, which was coupled with support from researchers, who buffered anxiety during periods of viral rebound. ATIs had a notable impact on personal relationships, including avoidance of dating, reduced intimacy and sexual pleasure while off ART. Easy access for partners without HIV to free PrEP, PEP, and condoms was welcomed by all participants. Restarting ART was difficult following the ATI, but was resolved with pre-trial preparation supporting adherence. The participants with lengthy ATIs remained enthusiastic but were challenged by uncertainty that required adjustment of their life plans. Finally, participants expressed mixed views regarding the use of placebo arms in trials but accepted a second ATI period after receiving broadly neutralising antibodies open-label.
Participants described being part of an ATI trial as both liberating and demanding. The findings indicate that acceptability is influenced by predictable, frequent weekly HIV viral load monitoring, timely results communication, and access to free prevention, with clear concerns about relationship impacts during viral rebound, and clearly communicated pre-defined ART restart criteria.