Participant Perspectives and Experiences Following an Intensively Monitored Antiretroviral Pause in the United States: Results from the AIDS Clinical Trials Group A5345 Biomarker Study
The AIDS Clinical Trials Group A5345 study (NCT03001128) included an intensively monitored antiretroviral pause (IMAP), during which participants living with HIV temporarily stopped antiretroviral treatment (ART) in an effort to identify biomarkers that could predict HIV rebound. We evaluated the potential impact of the IMAP on A5345 study participants in the United States by questioning them immediately after the IMAP and at the end of the study. We administered longitudinal sociobehavioral questionnaires to participants following the IMAP when they resumed ART and at the end of the study. We summarized descriptive data from the post-IMAP and end-of-study questionnaires. Open-ended responses were analyzed using conventional content analysis. Reactions to pausing ART involved a mixture of curiosity and satisfaction from contributing to science. All participants indicated adherence with the ART interruption. About half (9/17) of post-IMAP questionnaire respondents reported having sexual partner(s) during the IMAP, and of those, nearly all (8/9) did not find it difficult to use measures to prevent HIV transmission to partners. The majority believed that they benefited from the study, yet some had elevated anxiety following the IMAP and at the end of the study. Most (24/29) respondents who completed the end-of-study questionnaire would recommend the study to other people living with HIV. Our findings underscore the relevance of the psychosocial aspects of participating in studies that involve interruptions of ART. Understanding how participants experience this research is invaluable for informing the design of future research aimed at sustained ART-free virologic suppression.
Introduction
HIV cure-related research focuses on developing interventions that could completely eliminate HIV or confer sustained suppression of HIV in the absence of antiretroviral therapy (ART).1 Identifying biomarkers that accurately predict HIV rebound following ART cessation in people living with HIV (PLWH) would significantly advance the field.2,3 Intensively monitored antiretroviral pauses (IMAPs) have been performed to identify these biomarkers.4,5 For safety, careful clinical monitoring of PLWH is required during and following ART pauses,4 which usually involves frequent study visits and extensive biological sampling. Given the intensity of these study visits, participant-centered data are also necessary to inform how best to engage, recruit, and retain participants in HIV cure-related research.6
The ethical ramifications of pausing ART in PLWH—such as ensuring acceptable risks and monitoring procedures4,7–10—underscore the critical importance of collecting participant perspectives and experiences in HIV cure-related studies.4,6,11–19 Yet very few clinical studies involving HIV treatment interruptions have assessed participant perspectives and experiences. One study in Thailand revealed that PLWH wanted to interrupt ART in a safe and monitored environment,16 but were disappointed by the rapid viral rebound following ART interruption that they experienced.20 Another study in Belgium found high overall satisfaction of being in an HIV treatment interruption study and contributing to HIV cure-related science, despite underestimating the emotional impact of the treatment interruption.15
In a recent publication, we described reasons why participants living with HIV decided to undergo ART interruption in the multisite AIDS Clinical Trials Group (ACTG) study, A5345 (NCT03001128).19,21 A5345 included an IMAP, with the goal of finding biomarkers that could predict HIV rebound.22
As reported elsewhere,19 at baseline participants in A5345 viewed significant societal-level benefits of contributing to HIV cure-related research and helping the HIV community. Perceived personal-level benefits included the opportunity to learn about how one's own body responds during the IMAP.19 Building on these results, in this report we describe the perspectives and experiences of A5345 participants after the IMAP. Our objective was to gain insight into the potential impact of the IMAP on study participants through questionnaires completed immediately after the IMAP (at the ART restart visit) and at the end of the study (last visit or following viral re-suppression).
Methods
ACTG A5345 (A5345) study
The A5345 clinical study (NCT03001128) enrolled 61 participants from 2017 to 2020.22 The A5345 study included two cohorts as follows: (1) 46 participants diagnosed during chronic HIV infection (Cohort A) and (2) 15 participants diagnosed during acute HIV infection (Cohort B). A5345 aimed to identify biomarkers that would predict viral rebound among PLWH undergoing an IMAP. In the parent clinical study, there were 14 enrolling clinical research sites in the United States, as well as one in Puerto Rico and one site in Thailand. The A5345 protocol did not include any intervention, except for the IMAP. During the IMAP, the frequency of study visits was twice per week for the first 8 weeks and less frequently thereafter. The ART pause lasted ∼3 weeks on average (median time to viral rebound was 22 days).22 After pausing ART, participants were advised to resume ART and undergo a monitored period to document viral re-suppression if two consecutive HIV RNA measurements ≥1,000 copies/mL or two consecutive CD4+ T cell count <250 cells/mm3 were documented, among other criteria.