Participant experiences in a combination HIV cure-related trial with extended analytical treatment interruption in San Francisco, United States

Figures & data

Table 1. Post-ATI in-depth interview guide – participant experiences UCSF combination HIV cure trial (San Francisco, CA, USA, 2022–2023).

UCSF Combination HIV Cure Trial In-Depth Interview Guide – Post-Analytical Treatment Interruption (ATI) SECTION I: INTRODUCTORY QUESTIONS – PERSONAL BACKGROUND Are you back on your HIV medications? What was it like to be off your HIV medications for X days/weeks/months and now being back on them? What was the overall feeling you had while pausing your HIV medications? Were your expectations met or not? Please explain. What was the best part about being in this trial? What was the worst part? Do you have any concerns having completed the study? SECTION 2: KNOWLEDGE FACTORS Why you were asked to stop taking your medications? What did you learn about the trial that you did not know when you started? How do you think your participation impacts what we know about HIV cure-related research? At this time in the trial, how do you feel about the combination of interventions that you received? SECTION 3: DECISION-MAKING FACTORS Stepping back, how satisfied are you with your decision to participate in this study? What were the risks in your view? What were the benefits? How do you weigh them? SECTION 4: PSYCHOSOCIAL AND PARTNER FACTORS Overall, how are you feeling emotionally, right now, after you finished the treatment interruption? How did your viral load change during the study? Did you have any sexual partners during the study? What resources, information, or people, did you leverage to talk about risks of sex while off your HIV medications? What do you consider acceptable partner protection measures during the HIV treatment interruptions (e.g., PrEP referral for partners, etc.)? Is there anything else the study trial could have done to support you with partner protection? SECTION 5: CONCLUSIONS Do you have any recommendations to improve the conduct of future clinical trials like this one?

Table 2. Demographic Characteristics of UCSF combination HIV cure trial participants (San Francisco, CA).

Participant Identification Number	Age	Sex Assigned at Birth	Race and Ethnicity	Duration of ATI (days)
Post-ATI Interview Accepters
02	<50	Male	Declined to Answer, Hispanic	>300 days
03	>50	Male	White, Non-Hispanic	200-300 days
04	<50	Male	White, Hispanic	200-300 days
05	>50	Male	White, Non-Hispanic	100-200 days
06	>50	Male	White, Non-Hispanic	>300 days
07	<50	Male	White, Non-Hispanic	200-300 days
10	<50	Male	White, Hispanic	>300 days
Post-ATI Interview Decliners*
01	<50	Male	White, Hispanic	100-200 days
08	<50	Male	Declined to Answer, Hispanic	100-200 days
09	<50	Male	White, Hispanic	100-200 days

* 01 and 09 declined post-ATI interview due to time constraints. 08 declined post-ATI interview due to lack of privacy to conduct interview. To maintain confidentiality, only birth sex is indicated, as there was only one transgender individual in the study.

Table 3. Summary of considerations for implementing combination HIV cure trials with extended ATIs.

Decision-Making Factors PWH may have several motivations for joining complex combination HIV cure-related trials, such as mix of scientific altruism, trust in the clinical research, and hope of achieving post-intervention control. It is important to guard against potential therapeutic or curative misconception when enrolling participants in HIV cure-related trials. PWH’s backgrounds may influence their decision to participate (e.g., prior research participation or relationship with research team, time availability and resources to participate, personality types). Strategies will be needed to engage individuals in HIV cure-related trials who may not be as trusting of the clinical research establishment, with full-time responsibilities, or who are more risk-averse.

Trial Perceptions and Expectations Most participants perceived the likelihood of trial risks, although one participant was unable to accurately appraise risks. Close clinical monitoring mitigated potential worries around risks during the trial. Most participants perceived some trial benefits (e.g., psychosocial benefits such as sense of pride, purpose and optimism). Most participant had an accurate appraisal of the trial’s purpose and no expectation of being cured. However, it is possible that PWH still hope to be cured or achieve sustained post-intervention control. For participants whose HIV do not rebound, there can be confusion or uncertainty about their trial outcome.

Experiences with Combination HIV Cure Trial Trial teams should find a balance between the frequency of clinical monitoring visits and providing peace of mind for participants, and accommodate trial visits to participants’ unique circumstances when possible (e.g., travel schedules). There should be innovations in trial conduct to reduce trial intensity and burdens (e.g., home-based viral load test). There will be heterogeneity in how participants experience experimental interventions and procedures during the trial. There should an emphasis on safety and emotional health when undergoing experimental interventions. ATIs should be considered like a journey, on both physical and emotional levels. ATIs can be anxiety-provoking for participants who experience uncertainties around viral rebound. ATIs may not be as life-changing for participants who take daily pills for other medical conditions. Trial teams should carefully manage expectations around the state of durable ART-free control. Even the lack of viral rebound may not necessarily result in relief but can be a source of worry due to ongoing uncertainty. There should be a robust psychosocial infrastructure in place to take care of participants’ needs before, during and after ATI trials. Participants will experience ART restart differently (e.g., sense of relief, defeat). Research teams should emphasize that participants have not failed the trial when resuming ART, but have helped answer scientific questions. Customized approaches may be needed to support participants with ART re-adherence behaviors post-ATI.

Psychosocial Factors Becoming and remaining detectable for HIV during ATIs can be a stressor. ATIs are accompanied with viremia-related worry, which will likely increase with higher viral load measures. Viremia-related worry may be lesser for individuals with prior experience with prior HIV detectable status, but will need to be thoughtfully considered in the era of U = U.

Behavioral Factors There can be many challenges associated with partner protections during ATI trials (e.g., conversations around condom use, trying to find out if partners are on PrEP, helping partners navigate PrEP, dilemma around whether to have sex, taking oneself out of U = U. etc.). Evidence-based partner protections support in the context of ATI trials are needed for participants and partners.

Logistical Factors and Study Conduct Research teams should offer as much logistical support and flexibility to participants as possible. The importance of mental health, emotional and psychosocial support systems around each participant should not be under-estimated.