Participant Perspectives in an HIV Treatment Interruption Study in San Francisco, United States

Abstract

HIV cure-related clinical research studies often include analytical treatment interruptions (ATIs), in which participants pause antiretroviral therapy (ART). During ATIs, researchers closely monitor laboratory values and adverse events. We assessed and compared the perspectives of two distinct groups of participants: HIV noncontrollers and controllers in a San Francisco-based ATI study focused on identifying biomarkers predicting HIV viral rebound. Data were collected from 2021 to 2024 over five study time points to assess motivations, understanding of the study, decisional regret, and partner protections. All participants (n = 16) endorsed the goal of helping advance HIV research as a motivator, about half were also driven by interest in their body’s response to the ATI, and some indicated monetary compensation as a key motivator. Most participants (6 of 10 noncontrollers and 4 of 6 controllers) did not view personal health benefit as a primary study goal. All understood the option for an extended ATI if they had not met ART restart criteria after 28 days. At the study’s onset, all sexually active participants (n = 14) were informed about the risk of transmission to sex partners and the need for partner protections during ATIs. Among noncontrollers, 2 of 5 reported using condoms, being abstinent or partner use of preexposure prophylaxis (PrEP) during sexual activity. Among controllers, 3 of 5 reported sexual activity: one with a partner on PrEP, one with a partner on ART, and one using other protection methods. Decisional regret about study participation, measured on a scale of 0–100, was low among both noncontrollers (range 1.67–13.57), and controllers (range 8.33–10) during the ATI, and remained low following it (noncontroller M = 5.07, SD = 4.52; controller M = 10.00, SD = 11.31). Participants generally understood the study, highlighted the need for partner protection support during ATI, and reported low decisional regret.

Introduction

HIV cure-related research aims to understand the mechanisms of HIV persistence, eliminate HIV, or promote durable control of HIV in the absence of antiretroviral treatment (ART).¹ This includes identifying biomarkers that could predict when the virus will re-emerge in the blood and body compartments following ART interruption.^2,3 To support such research, people with HIV (PWH) are sometimes asked to temporarily discontinue ART—a study method called an analytical treatment interruption (ATI).⁴ ATIs involve carefully monitoring study participants’ laboratory values (e.g., viral load, CD4⁺ T cell count) and adverse events while they are off ART, with the expectation that the virus could re-emerge at any time.⁴ ATIs can range from weeks to months or even longer depending on a study’s goals. ATIs are used to identify individuals who can control HIV following standard-of-care treatment (“post-treatment control”) or an experimental intervention (“post-intervention control”). Other ATI studies seek to leverage ATIs to better understand the biology of HIV persistence.

Most PWH are noncontrollers—people who have high viral load set points in the absence of ART. In contrast, controllers can spontaneously control HIV without ART. This includes so-called elite or viremic controllers, who can maintain low or even undetectable levels of circulating virus prior to ART initiation. The current standard of care is for both noncontrollers and controllers to be treated with ART. Viral loads are generally expected to rebound to high levels within 2–4 weeks off ART, although there is a wide degree of natural variation.^5,6 Because of this, ATI studies require robust informed consent regarding potential risks and the need to protect sex partners from inadvertent HIV transmission during the viremic period.^4,7–9

To help respect those who agree to participate in this research, there is a need to better understand the perspectives and experiences of people undergoing ATIs.^4,10 For example, ATI participants from a study in Belgium reported overall high satisfaction from being part of the trial, but underestimated the burdens caused by ATIs, such as frequent invasive screenings.¹¹ In another study conducted in Thailand, participants were disappointed by the rapidity of their viral rebound.¹² In two studies in the United States,^13,14 ATIs were associated with anxiety from being off ART and difficulty managing sexual relationships, despite trust and support from the clinical team. A recent meta-analysis of 24 ATI studies (n = 382) found that over 95% of participants experienced viral rebound within 21 days following ART interruption, with sustained control beyond 12 weeks occurring in less than 5% of participants, highlighting both the rapid return of viremia following ART discontinuation and the rarity of prolonged ART-free control in the absence of intervention.¹⁵ Furthermore, recent research has documented the psychosocial experiences of ATI participants, including anxiety, partner transmission concerns, and shifting expectations during extended viral rebound periods.^13,16,17

As part of the Psychosocial and Ethical Aspects of HIV Cure-Related Research in the United States (PERSIST) project,¹⁸ we surveyed PWH during an observational ATI study (NCT00187512)¹⁹ at the University of California, San Francisco (UCSF), which did not include an investigational product. The primary goal of this UCSF SCOPE Analytic Treatment Interruption (SCOPE-ATI)²⁰ study (NCT04359186) was to investigate clinical and biological factors associated with viral rebound following an ATI, and to allow study of the earliest time points of viral rebound to better understand the immune responses that succeed or fail at controlling HIV in the long-term.

Our objective is to describe participants’ motivations, understanding of the study, partner protections during the ATIs, and decision satisfaction over the course of SCOPE-ATI. We also compare data between prior HIV noncontrollers and controllers.

Methods

Participants and procedures

Participants enrolled in the SCOPE-ATI study were recruited by the SCOPE-ATI research team to join this optional survey study. Inclusion and exclusion criteria for the parent study included being 18 years or older, willing to provide informed consent, having achieved ART suppression for at least 12 months, CD4⁺ T cell count > cells/lL, and having no significant physical or mental health problems. Participants on long-acting ART (i.e., cabotegravir/rilpivirine by monthly injection) were excluded because these agents can persist for months or years following a single administration due to their long half-lives, making it difficult to safely pause treatment due to risk of resistance emerging and to interpret rebound dynamics in the context of their long pharmacokinetic “tail.”

Participants were adults on ART, without co-infections, and able and willing to use protection with sex partner(s) at risk for acquiring HIV. All participants were informed that the goal of the ATI was to increase scientific knowledge around biomarkers that could predict the timing of viral rebound or the viral load set-point. A unique aspect of the study is that it enrolled both typical PWH who were noncontrollers prior to ART, as well as those who were known to be prior elite or viremic controllers but were on ART consistent with the clinical standard of care. Informed consent for the surveys was obtained prior to study participation in socio-behavioral study. As part of the study’s risk mitigation efforts, participants received ongoing risk-reduction counseling during all visits, including discussion of safer-sex practices (e.g., condom use, abstinence during detectable viremia), and counseling encouraging participants to help their partners access pre-exposure prophylaxis (PrEP) if indicated. While PrEP was offered upon request,⁸ qualitative data indicate there were challenges in partners navigating PrEP access,¹⁴ suggesting the need for more formalized partner-support pathways in future ATI studies.

Procedures in the SCOPE-ATI study consisted of a baseline period with 4 visits over 4–8 weeks, followed by the ATI phase with 3 visits per week for up to 4 weeks. Each visit included a blood drawing, symptom assessment, and a physical exam. A subset of participants underwent optional procedures, including gut biopsies, leukaphereses, and lymph node aspirations. Most participants resumed ART when they met the ART restart criteria, which included plasma HIV RNA >200 copies/mL, CD4⁺ T cells <350 cells/lL, acute retroviral syndrome, or at the request of the participant or their provider.

Participants known to be controllers prior to ART initiation were eligible for an extended ATI up to 26 weeks, based upon an assumption that they would re-achieve control. If a participant did not meet ART restart criteria by Week 26, they were eligible to continue monthly monitoring of ART after consultation with their primary care provider. ART restart criteria for controllers differed from noncontrollers only by the level and duration of viremia.

Data collection

The data collection period for the surveys lasted approximately 2 years, from October 2021 to January 2024. Surveys were administered, depending on participant availability, at five time points: 1) screening; 2) study initiation (day 0); 3) during the ATI (repeat surveys); 4) ART restart; and 5) end of study. These timepoints were strategically selected to correspond with critical trial milestones. The schedule was also informed by experience conducting similar psychosocial research in HIV cure-related ATI trials^16,17 and refined through interdisciplinary team discussions and community stakeholder input. During the ATI, all participants were surveyed at Days 7, 14, and 21. Those on an extended ATI were surveyed on Day 28 and then monthly. Survey content and modules varied by timepoint (Fig. 1). We used Qualtrics^XM to administer the surveys and manage the data. Qualtrics^XM was selected due to its secure data handling capabilities, customizable survey logic, and suitability for confidential selfadministration, which was done in effort to reduce social desirability bias and enhance consistency across repeated assessments. Noncontrollers and controllers completed similar surveys to allow comparisons.²¹

FIG. 1.

SCOPE-ATI survey content by module across timepoints.

Measures

Each key variable was assessed using structured survey items, drawing from validated tools whenever possible (e.g., decisional conflict and regret as described below),^22,23 and other instruments previously adapted and used in ATI-inclusive HIV cure research.²⁴ We collected demographic information, including gender identity, sex assigned at birth, age, Hispanic/Latinx ethnicity, race, education level, relationship status (all that apply), and annual household income (in $50,000 intervals).

Motivation and decision-making were measured via a multi-select checklist asking participants to identify reasons for joining the study (e.g., helping advance research, learning about body response, monetary compensation) and with whom they discussed participation (e.g., partner, family, HIV provider). Understanding of the study was assessed using multiple-choice items evaluating awareness of ATI goals, expectations for personal health benefit, and extended ART pause options. Perceptions of risks and benefits were captured with structured checklists covering psychological, physical, social, and financial aspects. Partner protection behaviors were measured at multiple time points using categorical questions on recent sexual activity, number of sex partners, and protection methods used (e.g., PrEP, condoms, abstinence, oral sex only), with “Other (specify)” and open-text options.

ART restart experiences were assessed via Likert-type responses evaluating comfort with restarting treatment and emotional reactions (e.g., relief, disappointment, fatigue), with qualitative elaborations where provided. Finally, end-of-study outcomes were measured using structured and open-ended questions about perceived personal benefit, negative effects, willingness to participate in similar studies, and suggestions for future improvement. Repeated assessments at multiple time points and confidential self-administration via Qualtrics^XM were used to improve consistency and minimize self-report bias.

Data analysis

We exported survey data from Qualtrics^XM and completed standard validation procedures. We generated frequency counts manually in Excel (version 2024) and by setting up cross-tabulations in Statistical Package for the Social Sciences (SPPS) version 28.0.1.1.²¹ When appropriate, “Other (Specify)” responses were re-coded from open-ended responses and included into existing categorical counts. Nonscaled variables were summarized using descriptive frequencies and proportions, stratified by prior noncontroller versus controller status and, when applicable, by study timepoint. We followed standard scaling procedures, detailed below, to calculate longitudinal scores for questions in the decisional regret survey module.

Scale scoring

Decisional conflict and regret.

Decisional conflict about study participation was scored at study start using a validated ten-item decisional conflict scale.²⁵ We scored decisional regret during the ATI and at end of study, using the procedure for scoring decisional conflict.²³ The decisional regret module consisted of five statements, three affirmative—“It was the right decision”; “The decision was a wise one”; “I would go for the same choice if I had to do it over again”— and two reverse-coded: “I regret the choice that was made” and “The choice did me a lot of harm.” Likert-scale response options were re-coded to numeric, ranging from 0 (strongly agree) to 4 (strongly disagree). We then computed mean scores per group and multiplied each by a factor of 25 to rescale to 100. A score of 0 indicates no decisional regret with higher scores indicating higher levels of decisional regret. We then plotted the scores across the relevant timepoints as a line graph.

Ethics statement.

The UCSF Institutional Review Board (IRB) reviewed and approved the UCSF SCOPE-ATI study and the survey sub-study (IRB #20–30442).

Results

Demographic characteristics

We surveyed 16 participants:

10 noncontrollers and 6 controllers. Sample size varied across visits. Participant ages ranged from 32 to 75 years. All but 1 participant self-identified as cisgender male. Most (12) were White/Caucasian and non-Hispanic/Latinx. There was a range of education levels: 5 participants had attended at least some college. Yearly annual income also ranged across all levels. About half (7) of participants were not currently in a relationship (Table 1).

Table 1.

Demographic Characteristics of SCOPE-ATI Study Participants, by Controller Status

Characteristic	Noncontrollers	Controllers	All
Gender identity
Man	9	6	15
Woman	1	—	1
Sex assigned at birth
Male	9	6	15
Female	1	—	1
Age (years)
30–39	1	1	2
40–49	3	1	4
50–59	3	3	6
60–69	2	1	3
70–79	1	—	1
Ethnicity
Hispanic or Latina/o/x	2	—	2
Not Hispanic or Latina/o/x	6	6	12
Prefer not to answer	1	—	1
Unknown	1	—	1
Race
Black or African American	—	1	1
White or Caucasian	8	4	12
More than one race	—	1	1
Other	1	—	1
Prefer not to answer	1	—	1
Education level
Some high school, no diploma	1	—	1
High school diploma or GED	3	—	3
Some college, no diploma	1	4	5
College degree (Bachelor’s)	1	1	2
Graduate degree or higher	3	1	4
Other	1	—	1
Relationship status (all that apply)
Single	5	2	7
Married	—	3	3
Divorced	2	—	2
Widowed	3	1	4
Domestic partnership	1	—	1
Other	—	3	3
Yearly household income (USD)
Less than or equal to $50,000	3	2	5
$50,001-$100,000	5	4	9
More than $100,000	2	—	2
Sample size	10	6	16

Motivations and decision making

Seven of 16 participants reported having discussed study participation with their partner(s) and more participants reported having discussed it with their family (11) and HIV providers (11) (Supplementary Table S1).

In addition, almost half of noncontrollers (5 of 10) considered monetary compensation as a main reason for participating, whereas almost all controllers (5 of 6) indicated an interest in their body’s response as a primary reason.

Understanding of the study

All participants who provided responses (14 of 16) understood the need for preventive measures (e.g., condoms or PrEP use) with sex partner(s) during the ATI (Fig. 2). Two selected not applicable (N/A) responses to indicate they were not sexually active.

FIG. 2.

Screening: understanding of the study, by controller status.

Noncontrollers.

While 6 of 10 understood that a direct benefit to their personal health was not a main goal of the study, some (3) believed this to be true (1 reported Don’t Know).

Controllers.

All (6) controllers understood that they had the option of pausing ART for a longer time, to determine whether spontaneous control would be re-achieved. Four understood that directly benefiting personal health was not a study goal.

Perceptions of the study (risks, benefits and concerns)

At screening, almost all participants (13 of 16) emphasized psychological benefits, and half (8) valued both physical and financial benefits (Fig. 3).

FIG. 3.

Screening—perceived risks, benefits, and concerns, by controller status.

Noncontrollers.

Perceived physical risks included significant changes to their immune system (4), having the virus come back (3), and the possibility of becoming resistant to HIV medication (3). Noncontrollers were primarily concerned about the physical risks associated with the ATI (3) and the required time commitments (3).

Controllers.

A third (2) indicated that there were physical risks associated with the ATIs and emphasized risk and concern about the virus coming back. All controllers (6) reported perceived psychological benefits, most (4) perceived physical benefits, and half (3) social benefits.

Decisional conflict and regret

At screening, participants reported that the decision to participate in the study was not hard to make, nor were they unsure what to do (Fig. 4a).

FIG. 4.

(a) Decisional conflict and decisional regret scores at study start (Day 0), by controller status. (b) Decisional regret scores during ATI and at end of study, by controller status. ATI, analytical treatment interruption.

Noncontrollers.

The mean decisional regret scores were low during the ATI, ranging from 1.67 to 13.57 on a scale of 0–100. Specifically, M = 13.33 (SD = 5.34), M = 13.57 (SD = 2.99), M = 1.67 (SD = 3.73), M = 2.50 (SD = 5.59). Scores remained low after the ATI M = 5.07 (SD = 4.52) (Fig. 4b).

Controllers.

The mean decisional regret scores were also low during the ATI, but flatter than those of the noncontrollers, ranging from 8.33 to 10 on a scale of 0–100. Specifically, M = 8.33 (SD = 9.77), M = 10.00 (SD = 6.97), M = 9.17 (SD = 6.85), M = 8.33 (SD = 10.21). Scores remained low after the ATI M = 10.00 (SD = 11.31) (Fig. 4b).

Partner protections

At study start, all participants (15) shared that researchers had explained how sex partners could be affected by study participation; about half (7) indicated having current sex partner(s) (data not shown). During the ATI, 5 of 13 participants reported sexual encounters within the last month, 4 reported one sexual partner in the last month, and 2 reported that their partners used PrEP (Table 2).

Table 2.

Partner Protections During ATI (Enacted ), by Controller Status

Characteristic	Noncontrollers	Controllers	All
Sexual encounter in the last month
No	5	2	7
Yes	2	3	5
Sex partners in the last month
One	2	2	4
Two	0	0	0
Three	0	0	0
More than three	0	1	1
Planned methods of partner protection in the last month (all that apply)
My partner(s) used pre-exposure prophylaxis (PrEP)	1	1	2
My partner(s) used post-exposure prophylaxis (PEP) if exposed to HIV	0	0	0
We used condoms during sex	1	0	1
We practiced only oral sex	1	0	1
We abstained from penetrative sex	1	0	1
Other	0	1	1
We did not use any protection methods (explain)	1	1	2
Withdrawal	1	0	1
Both HIV positive, partner ART adherent	0	1	1
Don’t know	0	0	0
Prefer not to answer	0	0	0
Anything study could do to help protect sexual partner(s) from HIV
No	0	2	2
Yes (provide PrEP)	1	1	2
Don’t know	1	0	1
Sample size	8	5	13

Noncontrollers.

Two of the 8 noncontrollers reported a sexual encounter during the last month. Their partner protection methods included PrEP, condoms, oral sex only, abstinence from penetrative sex, and withdrawal.

Controllers.

During the ATI, 3 of the 5 controllers reported sexual encounters during the last month, with either one (2) or more than three (1) partners. One reported their partner was on PrEP and another shared that their partner with HIV was adherent to ART.

ART restart

For most participants (9 of 12), resuming ART was successful and as expected (one participant did not answer this question) (Fig. 5). One participant who was a prior noncontroller expressed that their HIV was undetectable longer than anticipated. Another participant, who was a prior controller, shared that they were surprised at their fatigue levels during a viral load spike (data not shown).

FIG. 5.

ART restart—experienced risks and comfort with ATI and ART restart, by controller status. ART, antiretroviral therapy.

Noncontrollers.

All but 1 of the 8 noncontrollers were either very (5) or somewhat (2) comfortable with the reasons for starting ART. Similarly, all were at least somewhat or very comfortable with pausing HIV medication in a similar study in the future.

Controllers.

The 5 controllers reported mixed responses to being comfortable with reasons for restarting ART, ranging from “Don’t know” (1) and “Not at all” (1) to “Very much” (2). Almost all—other than 1 who reported “Don’t know”—were either somewhat or very comfortable pausing HIV medication in the future.

End of study

All respondents (14) reported that there were no negative effects from study participation and indicated feeling valued as participants. Most (10) noted that they benefitted personally from participation—especially, learning about their own physical response to the ATI (6) (Supplementary Table S2).

Noncontrollers.

The 9 noncontrollers reported a mix of feelings about restarting ART: relief (2), happiness (2), and disappointment (1). One reported improved daily pill adherence due to study participation, stating “I am better at taking them every day… because I needed to answer the question, have you missed any days”. Of those who reported personal benefits (6), most (4) listed learning about their own physical responses, and 1 indicated a social benefit, reporting meeting “nice, intelligent, straightforward people” (data not shown).

Controllers.

Almost all controllers (4 of 5) considered themselves to benefit personally from the study: learning about their physical response to the ATI (2), financially (1), and experiencing a sense of accomplishment (1).

Discussion

Our study offers novel insights into the lived experiences of participants undergoing an ATI with longitudinal psychosocial data collected at five study timepoints. While prior ATI trials have focused largely on biomedical outcomes, few have documented participant motivations, evolving understanding, partner protections and psychological responses in real-time.²³ Our findings contribute to a growing literature that emphasizes the ethical complexity of ATI trials. By enrolling both prior HIV noncontrollers and controllers, this study highlights how distinct clinical histories shape engagement, expectations, and reactions to ATI-related events such as viral rebound or ART restart. The inclusion of both groups enables a comparative lens that is rare in the ATI socio-behavioral research literature.

The consistently low levels of decisional conflict and regret across the study likely reflects the effectiveness of the informed consent process and support strategies used in SCOPE-ATI biomarker study. These findings replicate and align with the SEARCH RV411 trial in Thailand,²⁶ which also documented low decisional regret among ATI participants. Our study extends these insights by demonstrating that participant understanding of study purpose and risks can improve over time particularly when repeated opportunities for clarification are offered throughout the study.¹⁷ These findings also support emerging ethical frameworks advocating for ongoing informational exchange in HIV cure research, especially in protocols involving extended ATIs or nonstandard endpoints.²⁷ Unlike most studies that assess understanding, risks and regret retrospectively or at a single timepoint,^13,28 our longitudinal approach captures these constructs dynamically, revealing moments of initial uncertainty followed by increasing clarity and confidence in the findings.

Most SCOPE-ATI participants understood the need for partner protections during the ATI and, when relevant, took steps to reduce HIV transmission risk, including measures such as PrEP, condoms, or abstinence, which is consistent with prior research.^8,9 Research staff proactively explained how their sex partners might be affected during the study and provided participants with support to help mitigate the risks of unintended HIV transmission.^8,9 However, it is notable that two participants, one from each controller group, reported engaging in sexual activity during the ATI without any protective method. This raises ethical concerns regarding potential HIV transmission during extended ATIs. In addition, two participants requested the study provide PrEP for their partners, underscoring both the need and opportunity for enhanced structural support during ATIs. The need for support around partner protections was also identified in a hypothetical study involving diverse HIV serodifferent partners in the United States.^29,30 To strengthen future ATI protocols, standardized partner protection plans should be integrated, including access to PrEP, ongoing counseling, and behavioral monitoring. This is especially relevant as the field moves toward longer ATI windows and more diverse study populations, where risk perception and HIV prevention capacity may vary.^8,9,29,30 Ensuring consistent and proactive partner protection strategies is ethically important since they promise to help safeguard participants’ partners.

The psychological experiences surrounding ART restart further underscore the importance of individualized support during and after ATIs. While noncontrollers often expressed surprise and satisfaction with their ability to remain off ART longer than expected, some prior HIV controllers experienced fatigue, emotional distress, or disappointment when viral rebound occurred. These mixed responses highlight the need for ongoing guidance and support during ART restart to manage expectations and address potential concerns, as evidenced in other similar U.S. studies.^13,14 Importantly, our findings suggest that prior clinical identity, such as being an HIV controller may create distinct expectations that influence emotional responses to viral rebound and ART resumption. These expectations should be anticipated during study design and addressed through personalized pre- and post-ATI counseling. Of note, the clinical research team for the parent study emphasized a holistic, ‘journey-based’ approach to HIV cure during ATIs, providing continuous support and information throughout the study and follow-up, ensuring participants received guidance until they achieve viral re-suppression.

Taken together, our findings provide not only descriptive insights but also actionable guidance for the evolving design and ethical conduct of ATI-inclusive HIV cure trials. Our results underscore the need to move beyond traditional biomedical outcomes and incorporate participant-centered approaches that reflect the psychological and behavioral complexities of ATI research participation. Our longitudinal data demonstrate how participant understanding, decisional confidence, and partner protection strategies may shift over time, highlighting the importance of ongoing communication and real-time support rather than one-time informational interventions. These findings advance current understandings of ATIs by showing that participant experiences are not static but evolve alongside the study itself, especially in relation to ATIs and ART resumption. Our findings also contribute to a broader shift in the field toward trial models that embed psychosocial monitoring, formal partner protection measures (e.g., PrEP access and counseling),^9,31 and consideration of participants’ clinical histories and emotional readiness—that is, their psychological preparedness to navigate the uncertainties, stressors, and potential disappointments associated with pausing and resuming ART. By offering a comparative lens between prior HIV noncontroller and controller groups, we provide new evidence that individualized support strategies should help ensure ethical and inclusive participation. As ATI studies grow more ambitious in scope and duration, these findings highlight the need for trial designs that are not only scientifically rigorous but also grounded in the lived realities of people participating in HIV cure research. We summarized key implications emerging from this study in Table 3.

Table 3.

Key Takeaways and Considerations

Domains	Key takeaways and contributions
Participant understanding	• Understanding of study purpose and risks improved over time, reinforcing the value of continuous participant engagement.
Decisional confidence	• Longitudinal assessment revealed sustained low decisional regret, offering support for dynamic, ongoing informed consent over static, one-time evaluations.
Partner protections	• Participants showed willingness to protect sex partners, but some gaps in protective behavior highlighted the need to embed formal partner protection strategies (e.g., PrEP provision, counseling) as part of ATI protocols.
Emotional responses to the ATI	• ATI and ART restart elicited varied psychological responses particularly showing the importance of anticipatory counseling and tailored psychosocial support.
Clinical histories and expectations	• Differences between noncontrollers and controllers revealed how clinical histories shape trial experiences, emphasizing the need for personalized approaches in trial design and monitoring.
Implications for ATI trial design	• Findings support a shift toward participant-centered ATI studies that integrate psychosocial readiness assessments, embedded support services, and greater attention to participants’ relationships, social contexts, and caregiving responsibilities within protocol development.
Enhancing Representation and Generalizability	• Future ATI studies should aim to improve inclusion of underrepresented populations through community-based recruitment, culturally tailored engagement, and structural support (e.g., transportation, language access).
Future research directions	• While this study used structured survey instruments, future research should incorporate qualitative interviews in parallel to deepen understanding of participants’ experiences.

ATI, analytical treatment interruption.

Limitations

Our study has some limitations. First, the sample size was relatively small, in total and per noncontroller and controller group. While small sample size is a hallmark of early-phase HIV cure studies and may be unavoidable, we lacked the statistical power necessary to conduct more complex statistical testing comparing noncontroller and controller groups. As such, our findings are descriptive. Another limitation is the variable visit frequency during the ATI. While this is a feature inherent to the study design, it may be a confounder. That is, differences between groups may be attributable to differences in timing, rather than in controller status. The first three visits for both groups occurred approximately one week apart. However, later visits were more spread out, with intervals increasing as the ATI duration increased for the controller group (e.g., 2, 4, and 8 weeks apart). Another limitation is the demographic composition of our sample. Although the diversity of the parent study improved over time, those participating in this survey study were primarily older, White men. Of note, SCOPE-ATI enrolled cisgender and transgender women, as well as non-White participants; however, these participants were either enrolled prior to IRB approval or after the completion of the survey study. Although this is reflective of the participant population enrolled in the parent study and broadly consistent with demographic patterns in HIV cure-related trials,³² these findings should be interpreted with caution when considering their potential applicability to more diverse populations. Future studies should actively recruit participants across a broader spectrum of age, race, ethnicity, gender identity, and socio-economic backgrounds to enhance the inclusivity and generalizability of findings.^32,33

Conclusions

Our analysis of participants’ experiences in the SCOPE-ATI study showed that participants had high study understanding and generally adhered to partner protection measures and expressed a need for greater support to protect partners during ATIs. Longitudinal analyses revealed that participants had low decisional regret throughout the study. Initial comparisons between prior HIV noncontrollers and controllers indicate preliminary differences that could be explored through more robust methods, with larger sample sizes, in future research.

Supplementary Material

Supplementary Data