Altruism and contribution to science
Most participants expressed a desire to contribute to HIV cure research, emphasizing their willingness to participate even if they would not personally benefit. LTS viewed their involvement as a means to support efforts toward an HIV cure, recognizing the progress made in extending their lives and hoping to help future generations.
A lot of us hoped, especially long-term survivors… that we would live long… basically normal life and a lot of us have, and so [we would] like to be a part of something that could end up being a cure. – Cisgender Man, White.
If we don’t do the testing and research… how would we ever know if it might’ve helped someone in their final days? For me, the most important part is doing all these things you mentioned, so the next person might benefit. So yes, I would say I support it. – Cisgender Female, Black.
Some participants expressed a willingness to donate their tissues for interventional research at the EOL, with the understanding it would not cure their HIV or the terminal illness they faced. Others emphasized the broader significance of advancing HIV cure science, believing that many PWH in their position would be eager to contribute to efforts towards achieving durable virologic control without need of ART.
Scientific value and willingness to participate
LTS recognized the unique scientific value of conducting interventional studies at the EOL, believing that such research could lead to groundbreaking discoveries. They viewed this as an opportunity to contribute to HIV cure efforts in ways that traditional observational studies could not achieve. Participants opposed the exclusion of PWH at the EOL from interventional studies, arguing that it can reinforce HIV-related stigma and diminish their worth. They emphasized the importance of informed consent, believing that as long as PWH understand the risks, they should not be disqualified from participation. Some expressed openness to trying experimental interventions, if the risks were minimal.
I actually think it’s kind of stigmatizing to not allow me to participate in a study because basically, what you’re saying is, I’m at the end of my life, and I have no value anymore. – Cisgender Man, White.
Participants emphasized that PWH at the EOL should have the right to contribute to HIV cure research if they wish.
Unless there is overriding evidence that this is going to be harmful to me… there’s none of these that I think should be disallowed from somebody having the opportunity to try it. – Cisgender Man, White.
Autonomy and informed choice
Participants emphasized the importance of personal autonomy and the ability to make informed decisions about participation in interventional studies at the EOL. They believed PWH should have the right to decide whether to engage in such research, particularly when facing EOL decisions. Many participants stressed that decisions about research involvement should be left to the individual, provided they are mentally competent and fully informed.
It is my life; it is my choice. As long as I am mentally competent to make a decision, this is my choice, I mean, to knowingly go into a trial that may not help me. – Cisgender Man, White.
Participants highlighted the need for clear communication about the purpose and potential risks of EOL studies, emphasizing that discussions should be led by knowledgeable professionals. Beyond clinical monitoring, participants stressed the importance of emotional support in decision-making. They wanted clear communication to ensure that decisions were made by the individual. Some expressed openness to more invasive interventions if the risks were acceptable.
As long as I fully understand what I’m signing up for, there’s none of them that I think should be disallowed. – Cisgender Man, White.
By emphasizing autonomy, informed decision-making, and the right to weigh risks, participants reinforced the belief that individuals should have control over their participation in interventional HIV cure research at the EOL.
Acceptability of testing specific HIV cure research interventions at the EOL
Perceptions on testing LRAs at the EOL
While this section focuses on perspectives regarding the acceptability of testing LRAs at the EOL, several participants framed their views more broadly in relation to aging with HIV. For many LTS, aging and EOL were deeply interconnected experiences shaped by decades of illness, uncertainty, and treatment fatigue. As such, their concerns often reflected both the risks of LRAs for older people and their potential implications near the EOL.
Participants who supported LRA studies at the EOL emphasized their potential to advance HIV cure research. They viewed these studies as crucial for understanding HIV persistence and elimination, advocating for continued efforts to awaken and clear latent reservoirs rather than abandoning the approach.
I would be interested in it [LRA] because it would tell you something. – Cisgender Female, Mixed Race.
Skepticism about LRA studies emerged among participants who feared that reactivating latent HIV could trigger uncontrolled viral replication, threatening health and treatment stability. Participants who had maintained undetectable viral loads for years were particularly hesitant, citing concerns about viral adaptability and resistance.
To me, sounds like you’re wakening the beast. – Cisgender Man, White.
Why would I want to take a chance of my virus waking up and killing me? I’ve been undetectable since ‘97… If somebody wakes it up, and from what I know about the virus, it’s very smart… No, I would not do it. – Cisgender Female, Asian.
Others voiced broader concerns about reactivating latent pathogens, heightened vulnerability with aging, and increased risk of opportunistic infections. Given these uncertainties, several LTS suggested LRA studies should first be tested in younger, immunologically resilient populations before involving older PWH. Fears of a shortened lifespan and irreversible health effects deterred participation, suggesting potential recruitment challenges, particularly among older LTS.
The issue with latency-reversing agents is if they’re going to reverse HIV latency, which other pathogens that are latent might also have their latency reversed? They should perhaps only use latency-reversing agents if there’s already clinical data in younger participants. –, Cisgender Man, White.
Despite these concerns, some participants remained open to LRA studies, recognizing their scientific value. They were curious about how these interventions worked and viewed them as opportunities to deepen understanding of HIV persistence and latency reversal. Even while acknowledging the risks, they expressed interest in contributing to research that could ultimately benefit others.
Perceptions about block and lock approaches at the EOL
Many participants viewed block and lock as an innovative and potentially less risky HIV cure approach. Unlike other strategies that attempt to eliminate the virus, block and lock aim to suppress HIV indefinitely by keeping it in a dormant state. This concept resonated with several participants, who viewed it as an attractive and feasible method as it attempts to replicate exceptional elite control of HIV. Some expressed curiosity about how block and lock would work at a biological level and showed interest in its potential application.
I think that’d [block and lock] be a good approach. That’s interesting. I wonder how they would do that. Because then you’re getting into molecular biology. So and that’s really advanced, I would go for that one. Yeah. – Cisgender Man, White
Cisgender Man, White.Absolutely it’s [block and lock] less risky, perhaps… I think it’s certainly acceptable. I think it’s certainly something that people would do. I would. – Cisgender Male, White.
Participants questioned the feasibility and long-term effectiveness of block and lock strategies, particularly whether the “lock” would remain effective and if older PWH at the EOL would be included in research. Some found the concept unsettling, fearing the virus could eventually break free or cause unforeseen consequences. Despite skepticism, participants acknowledged potential benefits for some and supported continued research on block and lock approaches.
I mean, the thing with block and lock is how long does the lock remain effective? And I imagined researchers would want people who were relatively young and healthy… [T]hey [these studies] might not be particularly attractive to people who don’t have very long to live anyway. – Cisgender Man, White.
Perceptions about immune-based strategies at the EOL
Many participants strongly supported immune-based HIV cure strategies, reflecting their deep belief in the body’s natural ability to fight disease. They viewed interventions such as bNAbs and vaccine-based approaches as both promising and acceptable at the EOL, particularly given the absence of safety concerns. These strategies were seen as aligning with a broader interest in restoring or enhancing immune function, something participants noted was important for healthy aging and overall well-being. Some suggested that immune-based research could have broader relevance beyond HIV, including applications in cancer and other chronic illnesses.
It sounds particularly appealing to me, because I think that our bodies are pretty amazing. And I’ve always been all about, like, having a good healthy immune system… Maybe some of that work could translate into cancer research too. – Cisgender Female, White.
No problems with that at all. I see no particular problem. And using broadly neutralizing antibodies, and vaccine, vaccine therapies, those sorts of human-based services, definitely, they should be good. – Cisgender Man, White.
However, others expressed more cautious or mixed views. While intrigued by the concept, some questioned the relevance and safety of immune-based strategies for older adults, particularly given concerns about immune senescence. They called into question whether these interventions were better suited for younger populations and raised concern about the unintended effects of boosting the immune system, including the risk of inadvertently accelerating viral replication.
Well, I remember when I was newly diagnosed, they were saying that if you do something to increase your immune system, the virus also gets that system with it. So, does that mean the virus is going to be assessed to also to fight off? The T cell? I don’t know. Unless they can just do the T cell and not break that HIV. The virus in itself, but I don’t know how we’re done. – Cisgender Female, Asian.
Despite some uncertainties, participants generally viewed immune-based interventions with cautious optimism. Participants appreciated the immune-based interventions, especially if they could harness the body’s natural defenses to clear HIV without causing harm.
Perceptions about cell and gene approaches at the EOL
When asked about cell and gene-based interventions, most participants responded positively, expressing interest in contributing to research that could shape the future of HIV cure science. Although participants often used the terms interchangeably, their opinion involved a range of biomedical strategies, including cell therapies (modification of immune cells), gene therapies (genetic alterations to confer viral resistance), and gene editing technologies such as CRISPR. While these approaches differ in their scientific definitions with cell therapies involving cellular manipulation, whereas gene therapies directly target the genome, participants broadly regarded them as interconnected and promising avenues for advancing HIV cure research. Participants viewed the EOL context as an appropriate setting to test interventions that may be considered too risky for younger or healthier individuals. Some noted that long-term side effects were less of a concern at this stage of life, making older PWH uniquely positioned to support early-phase testing.
These would be ones that I think should be especially considered for end-of-life participants. Especially if they aren’t regarded as perhaps a little too risky to do in younger, healthier people. – Cisgender Man, White.
Yeah. I think these could be particularly valuable in older people, because some of the concerns are, you know, the off-target reactions, but if you’re at the end of life anyway, it’s, you know, the consequence of, you know, off-target effects might not be as great. So, yeah, I mean, the promise of, you know, the sort of gene editing approaches could have really dramatically effective responses. – Cisgender Man, White.
Participants voiced concerns about the safety and uncertainty of gene editing, with some unwilling to participate at the EOL due to unproven results and potential risks. Others were skeptical about its long-term effects and viewed it as a gamble. Ethical worries also emerged, with comparisons to designer genetics. Some LTS were willing to accept higher risks in HIV cure research, including gene therapy, emphasizing the need for testing and research to advance future clinical benefits for future generations of PWH.
Some participants questioned whether gene therapy would take effect quickly enough to produce a meaningful difference for PWH at the EOL. Given the advanced stage of illness, they expressed concerns that any potential therapeutic benefits might not manifest before death. This raised doubts for some about the personal relevance of participation.
I don’t, I mean, because you know, how long will it take for these [interventions] to show a difference in the person and in stage, before they die, before it takes effect. Does it make sense? You have to determine how long it’s going to take for to see show any progress. – Cisgender Female, Black.
Perceptions about combination approaches at the EOL
Participants strongly supported the scientific rationale for combination approaches in HIV cure research at the EOL, highlighting their potential to enhance effectiveness and reduce the risk of viral escape. While recognizing that these studies are not designed to offer direct clinical benefit to PWH at the EOL, many viewed participation as a meaningful contribution to advancing science. The concept of synergy, i.e. multiple strategies working together to achieve more than each could alone, was particularly compelling. Some participants pointed to prior success with combination ART as a model, suggesting that cure research should follow a similar path.
Right from the early days of combination therapy is that the combination of approaches are very likely to be the most effective, since it avoids all the mutation problems or minimizes the problem of viral escape. So, yes. Combination approaches should definitely be one of the ones that are considered. – Cisgender Man, White.
Yeah, that’s synergy, right? How things work together to be more than, you know, what they are separately. And that may be that’s where the treasure would lie in a synergistic approach. – Cisgender Female, White.
Some perceived that the EOL context was well-suited for testing these approaches, particularly if risks were monitored and the research design was clear.
I think the kitchen sink is needed. And as you get to the end of life, you know, we need to kitchen sink it. And I don’t think that people have that much of a reticence to engage in that. Because you know, it’s the end of your life. It’s all been a gift anyway, you had no life, you know, since 1995, it’s like, whoa, we’ve outlived our ticket. – Cisgender Female, Mixed Race.
Others voiced hesitation, citing the added complexity of multiple interventions, concerns about quality of life, and the limited time remaining to observe meaningful effects. For some, the idea of joining a more intensive protocol appeared burdensome, especially after years of managing other health issues.
It sounds too confusing, just to all of a sudden you got two things going on instead of just one. Yeah. And I’m sure it’s doable. But once again, the knowledge you have to get, but I would think, initially, I would say to you, that sounds a little confusing. I’m already doing three things. What more do I have to do now? You know, I used to just take two pills in the morning. So I hesitate. – Cisgender Man, White.
You know, it might, that medicine might have to take two weeks in my body. But if the person that’s end stage doesn’t have three days left, that’s not going to give me the accurate data that I’m looking for. – Cisgender Female, Black.
While some questioned the practicality of combination approaches at EOL, especially in advanced illness, others welcomed the opportunity to advance HIV cure science. Acceptability was shaped by perceptions of scientific value, personal capacity, and the clarity of the research design.
Ethical and practical considerations in interventional HIV cure research at the EOL
Generally, participants supported the opportunity to contribute to scientific progress, they also acknowledged the practical, physical, and ethical factors that must be addressed to ensure equitable and meaningful participation.
Diverse perspectives on ATIs during interventional trials at EOL
In the context of interventional HIV cure research at the EOL, many participants viewed ATIs as acceptable when framed as a contribution to scientific progress, rather than for personal clinical benefit. Participants understood that voluntarily stopping ART would help researchers better evaluate the impact of experimental interventions on viral rebound and reservoir activity. For some, the limited time left to live made participation in such studies and the risks involved reasonable, provided that the decision was voluntary and supported by clear communication and ethical oversight.
Several participants emphasized that PWH nearing the EOL should have the autonomy to discontinue ART if it no longer aligned with their personal goals for comfort or quality of life. Comparing this to decisions to stop chemotherapy or other treatments, they stressed that such choices should reflect individual values and priorities, especially at the EOL.
If they know that they’re going to die, why continue [ART] to take it? There is no need to keep taking it and [this] should be independent to take decision to do ATIs or not. – Cisgender Female, Black.
For others, ATIs were not only acceptable at the EOL but desirable under certain conditions. Some perceived ATIs as a means to ease the burden of lifelong adherence, reduce medication fatigue, or symbolically “let go” at the EOL. They noted that the risk of viral rebound was unlikely to result in significant discomfort or clinical deterioration within the limited time remaining.
If an end-of-life study participant is defined as somebody who is probably within six months of end of life, then really the risks of interrupting HIV treatment are really not very great, because I mean, even if there is a, you know, a major rebound of a virus, the risks are lower at the end of life. – Cisgender Man, White.
However, not all participants agreed. One respondent strongly opposed stopping ART near the EOL, citing fears of accelerated decline, worsening health, and the loss of the stability that ART had provided for decades. This view reflected a deep attachment to treatment and a desire to maintain as much physical control and well-being as possible, even in the final months of life.
Oh, no, they should never stop, never stop, you need to know. You’re on them for a reason. You know, you’re stopping and you’re deteriorating in your own body? – Cisgender Female, White.
Overall, participants held diverse views on ATIs at the EOL, with acceptability shaped by personal health, values, and a desire to contribute to HIV cure science, balanced against concerns about comfort, control, and the meaning of stopping ART.
Safeguards for ATIs in interventional research at the EOL
Participants who supported ATIs emphasized the need for safeguards to minimize risks. They stressed that any decision to stop ART should be clinically supervised, closely monitored, and, when possible, reversible to prevent unnecessary health deterioration. These measures were considered essential for maintaining trust and ensuring participant safety, even at the final stage of life.
What are my safeguards? Again, that’s something that you got to determine with each thing. As a non-scientist, I mean, I look at, for me, you know, how low are my T cells? How low is, you know, I mean, as they start getting down under 200, you know, it’s getting a little dicey there. – Cisgender Man, White.
There should be close monitoring and reversibility. So if the HIV is reactivated and begins affecting the T cells or other immune functions, there must be a way to reverse that. – Cisgender Male, Asian.
Physical and logistical challenges
Participants stated that an individual’s physical condition would determine their ability to engage in HIV cure research at the EOL, with some procedures, such as biopsies or apheresis, being too burdensome for those in declining health. Concerns were also raised about pain and discomfort, with some questioning whether undergoing additional procedures was worthwhile in their final days.
To do an apheresis or gut biopsy lymph donation that necessarily requires at least probably one day of inpatient. So that might just not be feasible at the end of life. – Cisgender Man, White.
Risk tolerance and participation in interventional trials
Some participants expressed a willingness to participate in high-risk experimental interventions, viewing them as an opportunity to contribute to scientific progress or as a final option for potential benefit. One participant emphasized that PWH at EOL may have little to lose, making them more receptive to interventional research.
You gotta have human trials. Right. And, and yeah, those of us who have reached that point where, you know, we’re beyond hope and we’re gonna die anyway.– Cisgender Male, White.
Despite this willingness, this participant acknowledged the deeply personal nature of such decisions, noting that the experience of discomfort significantly shapes perspectives on participation.
If you can make a body clear the HIV with a gene therapy, that doesn’t cause other problems… that to me sounds like something that would not increase suffering at the end of life. So… yeah, let’s try that. Yeah, let’s do that… Or, you know, I’m just done. I’m just worn out. I’m tired of the battle – Cisgender Male, White
And it’s, again, it’s very individual. – Cisgender Male, White.
This perspective highlights both the willingness to take risks in the pursuit of scientific knowledge and the importance of ethical considerations in involving PWH in interventional research at EOL.