Participant experiences in HIV cure-directed trial with an extended analytical treatment interruption in Philadelphia, United States

Figures & data

Table 1. BEAT2 trial scheme.

	Time period (weeks)	Study steps
Step 1	0	ART + Baseline evaluation (innate response measures, leukapheresis /rectal biopsy, ophthalmic evaluation) Qualitative Interview [6]
Step 2	4	ART + Pegintron injections
Step 3	26	ATI + Pegintron injections +  Broadly Neutralizing Antibodies Intravenous (IV) infusions
Step 4	12	ATI + Follow-up
Step 5	12	Return to ART, optional continued ATI Qualitative Interview

ART: antiretroviral therapy; ATI: analytical treatment interruption.

Table 2. BEAT2 participant experience study post-ATI interview guide.

What has been your experience in the clinical trial up to now? Let’s think about what you expected about being off HIV treatment when you first joined the clinical study. What were some of your original expectations of being in the clinical trial?  What, if any, have been some positive experiences that stood out to you during the clinical trial so far? What, if any, have been some negative experiences that have stood out to you during the clinical trial so far? You have just decided to return to taking your HIV treatments after taking some time off of them for the trial, correct? What was that like for you? How much time and effort do you feel you are putting into this clinical trial? What do you hope to get out of being in this clinical trial? What excites/excited you about being in this clinical trial? What worries/worried you about being in this clinical trial? At a time when we are all concerned about COVID-19, how has COVID-19 affected your trial experience? Do you have any recommendations for how we could improve the experience for people who participate in future clinical trial? Is there anything you would like from the research team at the end of the trial? What would you like the study investigators to know about your experience in this clinical trial?

Table 3. Participant demographics (age, race, sex).

Age		Race		Sex
30–40	2	Black	11	Male	11
41–45	2	White	3	Female	2
46–50	1	Asian	0	Trans (MtF)	1
51–55	4	Other	0	Total	14
56–60	5	Total	14
Total	14

MtF: male to female.

Table 4. Additional quotes—participant experiences in HIV cure-directed trials with an extended analytical treatment interruption (Philadelphia, United States, 2022).

Themes	Quotations
Overall experiences in the clinical trial
Motivations for continuing participation in the clinical trial
Adding meaning to their lives	The main reason why I want [to be in] this study [is] because it could actually take HIV out of somebody’s life, anyone’s life, out of the world, like, for good.
Contributing to scientific community	The study itself because this is cure research and I know that this is not going to cure me, but again if this is a step closer. I'm a part of history at this point so that’s exciting. Even if this particular study isn’t, the procedure is gonna [sic] be taken to do a cure. It was a contribution to the overall. So, I'm a part of history and it’s exciting.
Interest in trial conclusions	I was hoping that it would, you know, my blood work and be off meds, which would be a good thing, but maybe it would go on to some good results for somebody.
Change in expectations
Expectations changed in a positive way	Because first of, I didn’t think that I was going to qualify for it. Second of, I didn’t think I would last in it, because I just like everyone else, just knew every, I just thought of all the negative things, but once I decided to just to play it out, listen to see how it is and got in tune in all my personal questions were answered and I got to relax and like I said, I have a little bit more privilege than others… I'm going to say I had the pleasure and honor to participate, because everybody doesn’t qualify for it. So… I don’t have anything negative to say about this particular program.
Perceived and experienced side effects
Chills following infusion	I only had one set of… side effects. That was on my very first infusion, but that was something that I told I may or may not experience and that could go through the whole entire study… I just experienced cold chills and the people at the study site gave me a bunch of warm blankets. I was fine. It lasted maybe like 20–25 min.
Relieved did not experience negative health outcomes	I didn’t get sick. So, I know that it was possible to not be on medication and not really get sick from it or didn’t have any of the side effects that could’ve taken place. So, that was positive for me because, of course, you get a lot of leery when they tell you they’re taking you off the meds or they’re using this stuff to input into your body and what is it, what can happen, because they give you all the side effects that can happen; and to see that nothing happened, for me, that was a positive thing for me.
Perceived impact of clinical trial on mental and emotional health
Positive effects on mental and emotional health	Again, I think it’s about peace of mind number one. So, considering that during the study, I was monitored every week and that gave me peace of mind and then seeing my viral load stay undetectable for so long always make me feel like superman.
	This clinical study has helped give me self-confidence, encouragement. Before I got involved in this, I hadn’t worked in 14 years due to being ill, but they, I'm going to say, it helped give me back my life.
Perceived experiences with analytical treatment interruption
Perceived positive experiences from the ATI
Not having to take daily medications	It felt good, like it was, it’s hard to explain how good it feels not to take one pill… I didn’t have to take the HIV medicine. Every day I went without taking it, just makes it feel so good. I was just focused and keep going… Okay, I made it this long, good.
	I mean, it was nice to… not hav[e] to take a pill every day… I've stayed undetectable the whole time that I was on the study drug, and I mean, I don’t know, it was nice not to have to be on my medicine.
Remaining undetectable during the ATI	To a degree, I believe it was helping. I must say, I stayed undetectable for a long time, even off of my meds. So, I believe something was working and I don’t know what took place or transpired that caused it to jump, but I was off my meds for, I guess, about a year maybe and that was a year that was the longest I had been without my meds, since I started taking the medication. So, I guess it was doing its job.
Comfort in not having side effects during ATI	Nothing happened. I was well, I didn’t get sick… Well, I didn’t have any side effects. Let me say that I didn’t have any, nothing went wrong after coming off of my meds, I got to say, up until, at the end, towards the end of the whole trial for me that my viral spiked, but other than that, I was good. Even when the viral load spiked, I didn’t get sick, my CD4 count didn’t drop. Those were still good numbers. Just my viral load has spiked. So, other than that, everything else was good.
Perceived negative experiences from the ATI
Uncertainty related to increase in viral load	It’s been good for the most part, I think towards the end, a few weeks back, my numbers, my viral load jumped up high… unusual for me. So, it had me a little scared, because I had never seen my numbers in that area, in that range since I've been diagnosed. So, it kind of threw me a little bit. So, I was a little worried and made a decision to go back on my medication.
Monitoring of viral load eased anxiety	[The analytical treatment interruption] made me nervous at first, but I trust the process. We were monitoring my levels the entire time. So that did give me comfort, but it was still the idea of knowing that I would be off with my treatments long enough to get a little bit of a spike. So, I am a sexually active person so that made me – don’t put a pause on some things for a while, but other than that like I said, I really am interested in the study and the findings. So, I'm willing to do what I have to do to make sure we can get what we need.
Experiences with ART resumption
Relief with returning to HIV medications	As I mentioned earlier it gave me peace of mind, because like I said, I am undetectable… So, if I can’t do what I need to do to be healthy, then I have to put that on pause. So that part made me a little bit concerned. It didn’t take long before the PI [Principal Investigator] and the Study Coordinator were saying hey your levels are really high so let’s get back on treatment and once that happened, I was happy.
Appreciation for HIV medications	Right. Because, I took them for so many years, you kind of just take it for granted and then when you see those numbers change, and then you go back on it, and then you see the numbers go good again, you’re like, okay, this is, we took it for granted, because… everything was well until it wasn’t and then we saw it kick in, so.
Relationships with the clinical research team
Positive relationships with clinical research team	After dealing with the staff, I have to honestly admit, when going to my treatment and whatnot, they were so sweet, I mean, extra sweet. They were nurturing and they cared about their job. It wasn’t just a job for them and they would remember you by name.
Empathetic and caring response from clinical research team	I want to say this much, all of the staff and everyone… really made the bar very high for bedside manner, caring about how you [are] feeling. One day I went in the office, they could tell I was upset mentally, but physically I was doing okay, you know what I mean, and they made me take a moment to sit like, no, something [is] wrong. I was really having a major, major mental episode, and if it wasn’t for [the clinical research staff] and his staff, I would have been in probably driving and having a mental episode.
Effective communication during the ATI trial	No, I didn’t think too much about it. It was like, okay I met my appointments and they’re going over like my medical, not medical history but like what’s going on over my body. Everything was discussed right then and there and there was no alarm to me at that point.
Perceptions of trial procedures and logistics
Appreciation for clinical monitoring during the trial	I guess some of the positive things that came out of it was, because I was staying up with them, there was a lot of medical stuff that was taken care of, you know, blood pressure was taken on a regular I got the you know, the biopsy was done and you know, I went and got my eyes checked again, you know, difficult things like that I guess that was some of the positives that came off of it.
Transportation or parking issues	So, there were two different locations I would have to go to depending on what I was doing. Most of my study visits was a little bit more of a community finding. Parking was a lot of the times a hassle or public transportation. It took more to get there. The one that was closer, obviously that was easier because I could walk there.
Perceptions of compensation and effort
Perceptions of compensation
Compensation makes a difference	I really wasn’t doing it for money but HIV -- it doesn’t matter. I wasn’t doing it for money. That was making a difference.
Perceived effort
Minimal effort for the ATI trial	There wasn’t much time required. Like the times that were scheduled, like to travel or whatever… that is nothing, like putting the necessary time, but nothing extra, does that makes sense. And overtime, I didn’t waste any time, like I even count the transportation as part of the study.
ATI trial took time and effort	Well, it was a really big effort for me and my husband, because both of us live in [city name], which is almost to [state name], trying to get back and forth to doctor’s appointment, get to be much considering the fact, I do work two full time jobs… You know, all that kind of stuff took a toll on my job, and the distance it took to get here, and, you know, it was a bit much, but I would do it again.
Perceived effects of COVID-19
COVID-19 did not affect trial participation	They checked everybody and you had to, I know, at least [hospital name], you had to, they asked you questions before you came and they gave you a green pass that you had to answer the questions over your phone and they gave you a green pass, you showed that and they still checked your temperature, you didn’t sit near anybody and for the most part, the most people that I've ever had to sit in a waiting room was two others and we were nowhere near each other… So, like I said, I don’t have a bad experience.
Impact of COVID-19 on trial logistics	The only bad part was COVID-19. That’s what made it a little bit taxing. But it wasn’t this process of maintenance, but it was the COVID-19 precautions, the max, and because of COVID-19, the buses weren’t running as much. They were running on like a Sunday schedule, that was a little bit longer. That was the only kind of drawback, but that was beyond anybody’s control.
Suggestions to improve future HIV cure-directed clinical trials
Mental health assessments	I think you all could ask people when, even if they drop out, or if they complete the study and how did that experience like you doing now, affects you and if you are experiencing some type of depression for it, you can like recommend them, sure they do, but I'm saying, but that could be written in there that they do that and use people like myself to, you can ask them, because everything is not about a compensation, I want to say that because I know we talked, talked about that, but the reward would come from.

Table 5. Considerations for future HIV cure-directed clinical research generated in collaboration with BEAT-HIV Community Advisory Board.

Community-based participatory practice (CBPR) approaches can enhance socio-behavioral research practices embedded as part of HIV cure research efforts. HIV cure clinical trial participants are motivated by altruistic desires to help advance HIV cure science and the HIV community. It is important to manage participants’ expectations, focus on participants’ contributions, communicate uncertainty, and provide support to reduce feelings of having failed the research team and/or the HIV community following viral rebound. At the start of the clinical trial, it is important to provide information to participants that the trial is addressing an unknown question (e.g. whether the experimental intervention will have an impact on ability to keep HIV suppressed in the absence of ART) and will most likely not cure them. Providing regular and accurate information to participants during the trial is important to reduce the risk of therapeutic (or curative) misestimation or misconception. There should be adequate support for partner protections during the ATI (e.g. referral to of provision of pre-exposure prophylaxis (PrEP) for partners without HIV). It is important to emphasize time commitments, blood draws and procedures needed during HIV cure clinical trials. Participants’ experiences during ATI trials are heterogeneous. HIV cure clinical research teams should be attuned to participants’ tolerance for physical and psychosocial side effects. Capturing side effects from the participants’ perspectives can yield useful insight about how they experience clinical trials, and how to mitigate potential psychosocial risks during ATIs. Capturing participants’ lived experiences can complement biomedical assessments. The mental, emotional, and social impact of HIV cure-directed clinical trials on trial participants should not be underestimated. We recommend embedding frequent mental health checks as part of extended ATI trials involving viremia and ART restart periods, having health psychologists available as part of the trial team, and utilizing holistic person-centered clinical trial designs. Mental and emotional impacts can stem from the experimental interventions, ATIs (e.g. anxiety of being off ART) and even monitoring or additional procedures. Participants can be provided additional resources during the trial related to HIV or the ATI. We also recommend research teams to include some of the concerns of extended ATIs noted in this manuscript (e.g. anxiety of extended ATIs) as part of their informed consent forms. HIV cure trial participants must weigh the trade-offs of possible positive and negative effects of the ATI—e.g. not taking HIV medications vs. the worry of viral rebound and passing HIV to sex partner(s). Apprehensive feelings may be more prominent in people who have experienced undetectable HIV for many years. Close clinical monitoring and ongoing support from the clinical trial team are essential during the ATI and the period of viral load re-suppression to alleviate those feelings of worries. ART resumption following the extended ATI can be accompanied with both positive and negative feelings. These can include peace of mind from being on ART and can be mixed with disappointment about viral relapse. Some participants may need closer counseling and support with ART adherence following the ATI. Sensitization of medical providers of the time needed for viral re-suppression may be necessary. HIV cure trial participants value the relationships with and communications from the clinical trial team which can make a meaningful difference in their participation. Clinical trial teams should try to understand each participant’s unique circumstances during the trial. Trust is an important factor affecting retention in clinical trials. HIV cure trial participants may appreciate indirect or inclusion benefits, such as close medical monitoring. Clinical research teams should endeavor to reduce trial burdens and participation barriers as much as possible (e.g. offering ride share over public transportation). Adequate compensation makes participants feel appreciated and valued. It is important to disseminate data in lay terms to trial participants and community members following clinical trials. To help ensure meaningful involvement of critically under-represented groups in HIV cure research, we recommend adopting intentional social, racial and gender justice approaches to clinical trial designs and partnerships with community-based organizations well-versed in those issues.

Neergaard R, Jones NL, Roebuck C, et al. “I know that I was a part of making a difference”: participant motivations for joining a cure-directed HIV trial with an analytical treatment interruption. AIDS Res Hum Retroviruses. 2023;39(8):414–421.

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