Willingness of Older Canadians with HIV to Participate in HIV Cure Research Near and After the End of Life: A Mixed-Method Study

Abstract

HIV cure research requires interrogating latent HIV reservoirs in deep tissues, which necessitates autopsies to avoid risks to participants. An HIV autopsy biobank would facilitate this research, but such research raises ethical issues and requires participant engagement. This study explores the willingness to participate in HIV cure research at the end of life. Participants include Canadians with HIV [people with HIV (PWHIV)] aged 55 years or older. Following a mixed-method study design, all participants completed a phone or online survey, and a subset of participants participated in in-depth phone or videoconference interviews. We produced descriptive statistics of quantitative data and a thematic analysis of qualitative data. Barriers and facilitators were categorized under domains of the Theoretical Domains Framework. From April 2020 to August 2021, 37 participants completed the survey (mean age = 69.9 years old; mean duration of HIV infection = 28.5 years), including 15 interviewed participants. About three quarters of participants indicated being willing to participate in hypothetical medical studies toward the end of life (n = 30; 81.1%), in HIV biobanking (n = 30; 81.1%), and in a research autopsy (n = 28; 75.7%) to advance HIV cure research, mainly for altruistic benefits. The main perceived risks had to do with physical pain and confidentiality. Barriers and facilitators were distributed across five domains: social/professional role and identity, environmental context and resources, social influences, beliefs about consequences, and capabilities. Participants wanted more information about study objectives and procedures, possible accommodations with their last will, and rationale for studies or financial interests funding studies. Our results indicate that older PWHIV would be willing to participate in HIV cure research toward the end of life, HIV biobanking, and research autopsy. However, a dialogue should be initiated to inform participants thoroughly about HIV cure studies, address concerns, and accommodate their needs and preferences. Additional work is required, likely through increased community engagement, to address educational needs.

Introduction

Current HIV care relies on highly effective antiretroviral therapies (ART), with important benefits for the health and quality of life of people with HIV (PWHIV). PWHIV on ART have a life expectancy that is nearly comparable to the general population¹ and can attain a suppressed virology, thus eliminating risks of forward transmission.² Nevertheless, attaining and maintaining these benefits requires daily, lifelong ART adherence in addition to frequent blood work, monitoring, and clinical visits, with risks of long-term toxicities on certain tissues (e.g., kidneys and bone),³ and it is costly for health care systems and individuals.

Finding an HIV cure is challenged by the persistence of long-lived reservoirs within various anatomical sites, including the brain, lymphoid tissues (spleen, thymus, lymph nodes, etc.), bone marrow, lungs, kidneys, liver, adipose tissue, gastrointestinal tract, and genitourinary systems.⁴ Approaches to eliminate these reservoirs have focused on developing either a “complete⁵” cure, whereby all infectious HIV particles would be eliminated, or a “functional” cure, whereby a suppressed virology would be maintainable without ART.^6–8 For PWHIV, participating in HIV cure clinical trials implies an assessment of costs and benefits, possibly associated with having to stop ART and running the risk of developing resistances or transmitting HIV to others, and experiencing discomfort, side effects, or viral rebounds.⁹

Studying HIV reservoirs necessitates invasive procedures to obtain biopsies such as colonoscopy,^10,11 bronchoscopies,¹² and lumbar puncture,¹³ as well as riskier procedures seldom done for research purposes alone. The U.S. National Institute of Allergies and Infectious Diseases and the National Institute of Mental Health have set a new research priority to include terminally ill PWHIV in cure research.^14,15 An example is the Last Gift Study, conducted at the University of California-San Diego for PWHIV with a terminal illness and prognosis under 6 months.¹⁵ Participants donate ante-mortem specimens (e.g., blood, genital secretions) or their entire bodies as post-mortem specimens.¹⁵

Research autopsies to collect these specimens must be performed within 6 h of death, before virus and cell degradation.^16,17 In 2018 in Canada, a PWHIV expressed a strong interest to donate his organs to research and provided informed consent to a research autopsy. Various organs were processed for HIV cure studies in a timely manner.¹⁸ Following this paradigmatic case, the Canadian Enterprise for Cure Research (CanCURE)—an HIV reservoir and cure research collaboration—assembled to create the CanCURE HIV Autopsy Biobank.

As in any form of research, HIV cure research should maximize benefits, minimize risks, inform potential participants, and support voluntariness. Moreover, HIV cure research involving end-of-life and post-mortem procedures with PWHIV is a delicate topic raising specific ethical concerns^19,20 around potential participants' autonomy and vulnerability, possibilities of exploitation and next-of-kin/loves ones, and community acceptance.¹⁶

This study explores an understanding of HIV cure research, including clinical trials for an intervention or medication and end-of-life and post-mortem tissue donation for HIV biobanking and research autopsies. It aims at identifying the factors affecting willingness to participate, and the information needs of PWHIV who could be candidates for end-of-life HIV cure research. A secondary objective is to analyze the implications of quality of life on willingness to participate in HIV cure research and end-of-life procedures.

Methods

Design

Based at the Research Institute of the McGill University Health Centre (RI-MUHC), this study follows a cross-sectional mixed-method sequential convergent design, in which quantitative and qualitative data were consecutively collected and analyzed. It simultaneously collected and analyzed two independent strands of qualitative and quantitative data, and it used both result sets during interpretation to corroborate, confirm, or contrast findings.

Following a participatory approach, community stakeholders were involved, contributing their expertise and experiences, optimizing knowledge dissemination, and promoting access to participation. Two community members, a PWHIV, and a Montreal-based community organization representative were included as co-investigators. Along with the CanCURE Community Advisory Board (CAB), which includes community representatives from across Canada, they were consulted and involved at all steps of the study.

This study received approval of the Research Ethics Board of the RI-MUHC (2020-6030) on April 15, 2020.

Participants

We recruited participants via a convenience sample of PWHIV. During regular medical appointment at the Chronic Viral Illness Service of the MUHC, Montreal, and at the Maple Leaf Clinic, Toronto, health care professionals gave eligible patients basic information (research theme, main methods, duration of participation) and referenced those wanting more information to the study coordinator. Both these clinics are specialized in HIV clinical care. Further, advertisements were placed on the bulletin boards at the Centre Hospitalier de l'Université de Montréal infectious diseases/HIV clinic. We also recruited participants using the CanCURE CAB listservs, and the study was also advertised on the CanCURE website (https://www.cancurehiv.org).

Inclusion criteria included: being diagnosed with HIV-1 for at least a year, being 65 years old or older (later adjusted to 55 years old due to difficulties in recruitment due to COVID-19 prevention measures), or being diagnosed with a terminal illness, living in Canada, and being able to speak and understand either French or English. People could participate regardless of whether they were on ART.

Theoretical framework

This study is partly informed by the Theoretical Domains Framework (TDF), which makes the theory of behavioral change more accessible to implementation researchers to identify barriers and facilitators to interventions.^21–23 The TDF includes 14 domains to explain the impact of experiences, resources, and constraints on how individuals or communities perceive and act. These domains are categorized into three constructs: capability (knowledge, skills, behavior regulation, memory and attention, decision making), opportunity (environmental context and resources, social influences), and motivation (goals, social/professional role/identity, beliefs about capabilities, beliefs about consequences, optimism, reinforcement, emotions).²¹

Data collection

All participants were invited to complete a survey in French or English. The survey was adapted from instruments used in the Last Gift study²⁴ to allow comparisons between United States and Canadian results and to promote collaboration between the two initiatives. The survey gathered demographic data (e.g., age, gender-identity, race and ethnicity, marital status, household income, education, religious affiliation and current perception of health), and details regarding HIV status, time of diagnosis, and experience with ART.

Participants were also asked general (yes-no) questions about their willingness to participate in HIV cure research toward the end of life (e.g., clinical trials), HIV biobanking (the act of banking specimens on a potentially long term, whether they are collected pre- or post-mortem), and undergoing a research autopsy; possible perceived risks of participating in HIV cure research at the end of life; possible motivations and concerns related to HIV biobanking; and possible perceived risks associated with a research autopsy. They were asked to rate the perceived benefits of these types of research on scales ranging from 1, “Not true at all for me,” to 5, “Completely true for me.” They also rated the added meaning of these types of research to their life from 1, “Not at all,” to 5, “Very much.”

Participants who agreed during consent were contacted after the survey to participate in an in-depth qualitative interview in French or English, until saturation was reached. Interview schedules were designed to collect more detailed and frank perspectives from participants and to contextualize quantitative survey results (see supplementary material). One interviewer with extensive training and experience in qualitative methods conducted all interviews. Interviews lasted about 1 h and included open-ended questions on participants' understanding, perceived risks and benefits, and need for more information concerning HIV cure research, tissue donation for HIV biobanking, and research autopsy.

Different administration modes were offered to accommodate participants and to respect COVID-19 prevention measures, which prohibited face-to-face interviews. During the informed consent process, participants were asked whether they wanted to answer the survey individually on paper or on a computer, or whether they wanted the questions to be asked by a research staff by phone or videoconferencing. In-depth interviews could take place by phone or videoconferencing.

Data analysis

We generated descriptive statistics on sociodemographic characteristics, interest in participating, motivations and concerns, perceived benefits and risks, perceived added meaning to one's life, and willingness to risk shortening one's life and to donate tissues. To meet our secondary objective, we compared results for participants who reported a low or neutral quality of life (rated 3 or less on a scale of 1–5) and those who reported a good or very good quality of life (rated 4 or 5).

Interview recordings were transcribed and then revised and de-nominalized by D.L. D.L. conducted an inductive–deductive content analysis of both French and English transcriptions using the NVivo 12.0 software (Melbourne, Australia). D.L. inductively coded and categorized participants' answers with respect to their understanding and perception of HIV cure research, barriers and facilitators to participation in HIV cure research, HIV biobanking and research autopsy, in addition to the need for more information.

Identified themes concerning barriers and facilitators to participation were then themed within the TDF. Illustrative quotes in French presented in this manuscript were translated to English. To ensure reliability, preliminary results were discussed with C.T.C. and K.D., and then with members of the CanCURE CAB and co-authors.

Results

Quantitative results

From April 2020 to August 2021, 48 potential participants were referred to the study coordinator, of whom 37 (77%) completed the survey, and 15 of them participated in an interview. All participants were 55 years of age or older, with a mean age of 69.9 years, and living with HIV for a mean of 28.5 years. Most participants were men (n = 32; 86.5%), white (n = 34; 91.9%), born in Canada (n = 30; 81.0%), and had at least a college degree (n = 29; 78.3%). About a third of participants were single (n = 12; 32.4%), and some had children (n = 5; 13.5%).

Table 1 shows the sociodemographic characteristics for all participants (n = 37), stratified by rated quality of life, and for those who participated in qualitative interviews (n = 15). Compared with participants who reported a low or neutral quality of life (n = 8), relatively fewer participants who reported a good or excellent quality of life had disclosed their HIV status to at least some family members (n = 15, 51.7% vs. n = 7, 87.5%), and a greater proportion of them identified with a religious affiliation (n = 13, 46.4% vs. n = 2, 25.0%).

Table 1.

Sociodemographic Characteristics of All Included Participants (N = 37), Participants in Interviews (n = 15), and Stratification by Reported Level of Quality of Life

	Total, N = 37	Reported quality of life		Participants in semi-structured interviews (n = 15)
		Low or neutral, N = 8	Good or excellent, N = 29
Age
Mean (SD)	69.9 (5.9)	69.6 (3.8)	70.0 (6.4)	69.4 (7.15)
Median (IQR)	69 (66.5–73), Missing = 1	68.5 (67–71.5)	69.5 (65.5–73.0), Missing = 1	69 (66–71.5)
Gender, N (%)
Male	32 (86.5)	7 (87.5)	25 (86.2)	11 (73.3)
Female	5 (13.5)	1 (12.5)	4 (13.8)	4 (26.7)
Ethnicity, N (%)
Caucasian or White	34 (91.9)	8 (100)	26 (89.7)	13 (86.7)
Black, African, or Caribbean	2 (5.4)	0	2 (6.9)	2 (13.3)
Indigenous, First Nations, or Metis	1 (3.5)	0	1 (3.5)	0
Immigration status, N (%)
Born in Canada	30 (81.1)	7 (87.5)	23 (79.3)	12 (80.0)
Born in another country	8 (18.9)	1 (12.5)	6 (20.7)	3 (20.0)
Education, N (%)
High school or less	8 (21.6)	2 (25)	6 (20.7)	4 (26.7)
Collegiate degree	22 (59.4)	5 (62.5)	17 (58.6)	8 (53.3)
Professional or graduate degree	7 (18.9)	5 (12.5)	6 (20.7)	3 (20.0)
Marital status, N (%)
Single never married	12 (32.4)	1 (12.5)	11 (37.9)	6 (40.0)
Married or common law partner, without children	10 (27.0)	1 (12.5)	9 (31)	3 (20.0)
Married or common law partner, with children	5 (13.5)	2 (25)	3 (10.3)	2 (13.3)
Divorced or separated	9 (24.3)	4 (50)	5 (18.2)	2 (13.3)
Widowed	1 (2.7)	0	1 (3.5)	1 (6.7)
Religious affiliation, N (%)
Yes	15 (41.7)	2 (25)	13 (46.4)	7 (46.7)
No	20 (55.6)	6 (75)	14 (50)	7 (46.7)
I prefer not say	1 (2.8), Missing = 1	0 (0)	1 (3.6), Missing = 1	1 (6.7)
Number of years with HIV
Mean (SD)	28.5 (7.9)	26.2 (10.3)	29.2 (7.2)	31.1 (7.6)
Median (IQR)	31 (24–34)	26.5 (17–36.5)	31 (26–34)	33 (28.5–35.5)
Disclosure with family members, N (%)
Did not tell family	8 (21.6)	1 (12.5)	7 (24.1)	3 (20.0)
Told one family member	7 (18.9)	0	7 (24.1)	1 (6.7)
Told some family members	13 (35.1)	4 (50)	9 (31.0)	6 (40.0)
Told all family	9 (24.3)	3 (37.5)	6 (20.7)	5 (33.3)
Past participation in research on an HIV treatment, N (%)
Yes	20 (55.6)	4 (57.1)	16 (55.2)	5 (33.3)
No	10 (27.8)	2 (28.6)	8 (27.6)	6 (40.0)
Do not know/Do not remember	6 (16.7), Missing = 1	1 (14.3), Missing = 1	5 (17.2)	4 (26.7)

IQR, interquartile range; SD, standard deviation.

Table 2 shows the results of willingness to participate, perceived benefits and risks, motivations and concerns, and perceived added meaning to one's life relative to the three types of HIV cure research considered (research toward the end of life, HIV biobanking, and research autopsy), for all participants and by rated quality of life. At least three quarters of participants expressed willingness to participate in the three types of research: research toward the end of life (n = 30, 81.1%, vs. n = 1, 2.7% unwilling and n = 6, 16.2% uncertain), HIV biobanking (n = 30, 81.1%, vs. n = 3, 8.1% unwilling and n = 4, 10.8% uncertain), and research autopsy (n = 28, 75.7%, vs. n = 5, 13.5% unwilling and n = 4, 10.8% uncertain). There were no large differences seen in willingness to participate in each research type according to quality of life.

Table 2.

Participants' (N = 37) Willingness to Participate in HIV Cure Research, and Perceived Benefits and Meanings, and Stratification by Reported Quality of Life

	Total, N = 37	Reported quality of life
		Low or neutral, N = 8	Good or excellent, N = 29
Participation in HIV cure research at the end of life
Willingness to participate, N (%)
Yes	30 (81.1)	7 (87.5)	23 (79.3)
No	1 (2.7)	0	1 (3.5)
Do not know	6 (16.2)	1 (12.5)	5 (17.2)
Perceived benefits, mean (SD)
My participation would benefit science and society	4.7 (0.7)	4.3 (1.2)	4.8 (0.5)
I would hope to personally benefit from participating	3.4 (1.4)	3.5 (1.4)	3.3 (1.4)
My participation would benefit biomedical research	4.6 (0.9)	4.4 (1.1)	4.7 (0.8)
I would participate because it would benefit a greater cause	4.5 (0.8)	4.3 (1.0)	4.6 (0.7)
I would participate because it would benefit me	3.1 (1.6), Missing = 1	3.3 (1.8)	3.0 (1.6), Missing = 1
I would participate because I wanted to give back	4.4 (0.9)	4.1 (1.0)	4.4 (0.9)
Perceived risks, mean (SD)
Possible unpleasant side effects	21 (61.8), Missing = 1	5 (71.4), Missing = 1	16 (59.2), Missing = 2
Large blood draws that I would need to donate	7 (20.6), Missing = 1	1 (14.3), Missing = 1	6 (22.2), Missing = 2
Decrease in quality of life	11 (32.3), Missing = 1	1 (14.3), Missing = 1	10 (37.0), Missing = 2
Physical pain	11 (33.4), Missing = 2	2 (33.3), Missing = 2	9 (33.3), Missing = 2
Not being cured of HIV	7 (20.6), Missing = 3	3 (42.9), Missing = 1	4 (14.8), Missing = 3
Possible permanent or irreversible side effects.	14 (41.2), Missing = 3	2 (28.6), Missing = 1	12 (44.4), Missing = 2
Possible impacts on health coverage	8 (23.6), Missing = 3	0 (0.0), Missing = 1	8 (29.6), Missing = 2
Feeling vulnerable at the end of life	15 (45.4), Missing = 4	4 (66.7), Missing = 2	11 (40.7), Missing = 2
Being taken advantage of	6 (18.2), Missing = 4	0 (0.0), Missing = 1	6 (23.1), Missing = 3
Perceived added meaning to one's life, mean (SD)	3.4 (1.2)	3.5 (1.2)	3.4 (1.2)
Willingness to shorten one's life to participate in medical research, mean (SD)	2.2 (1.5)	2 (0.9)	2.2 (1.6)
Participation in HIV biobanking
Willingness to participate, N (%)
Yes	30 (81.1)	6 (75)	24 (82.8)
No	3 (8.1)	0	3 (10.3)
Do not know	4 (10.8)	2 (25)	2 (6.9)
Perceived benefits, mean (SD)
My participation would benefit science and society	2.4 (1.6)	2.4 (1.5)	2.4 (1.6)
I would hope to personally benefit from participating	1.8 (1.3)	1.8 (1.0)	1.9 (1.4)
My participation would benefit biomedical research	4.5 (0.9)	3.9 (1.0)	4.7 (0.8)
I would participate because it would benefit a greater cause	4.6 (0.9)	4.0 (1.1)	4.7 (0.9)
I would participate because it would benefit me	2.3 (1.5)	2.4 (1.3)	2.2 (1.6)
I would participate because I wanted to give back	4.2 (1.2)	4.0 (0.9)	4.2 (1.3)
Motivation to participate, N (%)
To help other/future people living with HIV	25 (67.6)	6 (75)	19 (65.5)
To advance scientific knowledge	25 (67.6)	4 (50)	21 (72.4)
To improve my own care	4 (10.8)	1 (12.5)	3 (10.3)
To help a member of my family, a loved one	1 (2.7)	1 (12.5)	0
Concerns about participation, N (%)
Concerns for the privacy of your data	6 (16.2)	1 (12.5)	5 (17.5)
A lack of self-benefit	1 (2.7)	0	1 (3.5)
Too great of a commitment	3 (8.1)	0	3 (10.3)
Physical discomforts (e.g., needlestick)	11 (29.7)	1 (12.5)	10 (34.5)
Perceived added meaning to one's life, mean (SD)	3.4 (1.2)	3.6 (1.3)	3.3 (1.2)
A research autopsy being performed
Willingness to participate, N (%)
Yes	28 (75.7)	5 (62.5)	23 (79.3)
No	5 (13.5)	1 (12.5)	4 (13.8)
Do not know	4 (10.8)	2 (25)	2 (6.9)
Perceived benefits, mean (SD)
My participation would benefit science and society	4.3 (1.1)	4.3 (1)	4.3 (1.2)
I would hope to personally benefit from participating	2.1 (1.6)	1.9 (1.4)	2.2 (1.7)
My participation would benefit biomedical research	4.5 (1.1)	4.1 (1)	4.6 (1.1)
I would participate because it would benefit a greater cause	4.4 (1.1)	4.3 (1)	4.5 (1.1)
I would participate because it would benefit me	1.8 (1.4)	1.4 (1.1)	1.9 (1.5)
I would participate because I wanted to give back	4.0 (1.3)	4.1 (1)	4 (1.4)
Perceived risks, N (%)
Being recognized as someone living with HIV	3 (8.6), Missing = 1	0, Missing = 1	3 (10.7), Missing = 1
Being treated poorly by study staff	4 (14.3), Missing = 1	0, Missing = 1	4 (14.3), Missing = 1
Having my health information not kept confidential	8 (22.9), Missing = 1	2 (28.6), Missing = 1	6 (21.4), Missing = 1
Perceived added meaning to one's life, mean (SD)	3.1 (1.4)	3 (1.3)	3.2 (1.4)
Willingness to give a part of the body to research following one's death, mean (SD)	3.7 (0.9)	3.9 (0.6)	3.7 (0.9)

Concerning perceived benefits, little to no differences were noted in the stratification by rated quality of life. For the three types of research, the two items on “altruistic” benefits (i.e., benefiting science and society, biomedical research, or a greater cause, and giving back) were rated higher, on average, than those on “personal” benefits. “Personal” benefits were rated higher for participation in HIV cure research toward the end of life (respective averages of 3.4 and 3.1 on Likert scale) than for HIV biobanking (1.8 and 2.3) and research autopsy (2.1 and 1.8). Likewise, about two-thirds of participants (n = 25, 67.6%) expressed “altruistic” motivations (i.e., help other/future PWHIV and advance scientific knowledge) to HIV biobanking, which are substantially higher proportions than for more personal motivations.

Also, the average rating of perceived benefits for science and society of HIV biobanking were lower (2.4) than for research toward the end of life and research autopsy (both rated 4.3). The average rating of perceived added meaning to life was of 3.1 for research autopsy and 3.4 for research toward the end of life and HIV biobanking.

Concerning perceived risks of HIV cure research toward the end of life, more than a third of overall participants expressed feeling vulnerable (n = 15; 45.4%), and two thirds (n = 4; 66.7%) for participants reporting a low or neutral quality of life. More than a third of participants expressed concerns for possible permanent/irreversible side effects (n = 14; 41.3%), and physical pain (n = 11; 33.4%), and more than half of participants (n = 21; 61.8%), for unpleasant side effects. This proportion reached almost three quarters for participants who rated their quality of life low or neutral (n = 5; 71.4%). Also, almost a third (n = 11; 29.7%) of participants expressed concerns for physical discomfort with HIV biobanking. Finally, about a fifth of participants (8; 22.9%) expressed concerns about “having their health information not kept confidential” during a research autopsy.

Qualitative results

Perceptions of participation in end-of-life HIV cure research

Qualitative analyses of participants' perceptions of end-of-life HIV cure research identified three themes, presented in Table 3 with illustrative quotes. First, participants perceived research as a Contribution to progress in health and science. They considered enrolling in research as a contribution to the advancement of knowledge on HIV and other health conditions (e.g., cancer) and to the improvement of PWHIV's well-being, via the improvement of care and medication. Second, participants perceived research as an Opportunity to learn more, that is, an opportunity to access new information on HIV, medication, or health management, which could help one accept and manage their condition.

Table 3.

Participants' Perceptions of End-of-Life HIV Cure Research

Theme	Illustrative quotes
Contribution to progress in health and science	[For example,] I cannot go on without insulin. But I do not have to use it because there was research and they discovered new molecules for diabetes. So research allows this [kind of breakthroughs]. (Man, 69 years old) [Research helps] people understand an issue. I think it's a little bit like mining and then you discover the benefits of [results] and then you use the data. It's a dynamic aspect to human progress. (Man, 77 years old) I feel like doing research to find a cure for HIV would also help find a cure for other diseases too because I tend to suspect there's a relationship between finding a cure for HIV and finding a cure for cancer. Maybe I'm not very scientific about it but I sort of hypothesize there's some sort of relationship in there. (Man, 73 years old)
Opportunity to learn more	I'm interested in what they're researching, in who's involved, and what kind of information they're going to get out of all the data that they're collecting. And I'm immediately motivated to be involved with it because it's a way for me to learn more about myself and HIV. Learning is a motivation. (Woman, 67 years old) Research to me means finding out information that will help people with some of the barriers that they have like, like treatment issues or getting access to treatment. […] It can help you understand when you get a diagnosis that you really don't want to hear and you don't know how to deal with it. (Woman, 55 years old)
A gift back to the community and to younger generations	[Participating in research] is a way of showing appreciation for all those who have been involved in research since the very beginning. It's because they were involved in research that some of the solutions that I have grown to benefit from exist. So, it's a way of giving back to a community that has already given me so much. (Woman, 67 years old) Benefits [of research] may not be in our lifetime. It holds answers for the future, and this way it's like giving back to society or to the community, even after my life is gone. I've lived all these years so. When my time is up, I'll be at peace, but I could still give back and contribute, and it would give me value and importance. (Woman, 64 years old) I will not have an advantage [from research] because I will be dead. Any advantage will be been lost when if die before there's a cure. The only advantage would be that I would have played some role in developing a cure for those in the future. (Woman, 67 years old)

Third, they perceived participation as a Gift back to the community and to younger generations. As PWHIV who had managed to stay relatively healthy, participants expressed a sense of duty regarding research. For them, their participation contributed to the collective well-being, mostly in the future, when results (e.g., effective HIV cure strategies) would be implemented.

Barriers to participation

Table 4 presents barriers, with illustrative quotes, to participation in end-of-life HIV cure research, which were distributed across four TDF domains—environmental context and resources, social influences, beliefs about consequences, and beliefs about capabilities—encompassing eight themes.

Table 4.

Illustrative Quotes to Barriers to Participation in End-of-Life HIV Cure Research, Categorized by Theoretical Domain

Theoretical domain	Barrier	Illustrative quotes
Environmental Context and Resources	Having had a difficult or painful experience with research and care	Before, I was ready for anything, but I had a problem in a research. They injected me something in the knee or in the thigh, and I had a bad reaction. Still today, I have after-effects. (Man, 71 years old) If I hadn't had so many bad reactions from medication, I would probably be more somebody that would try. Especially… But, I mean, now that I found the [medication] that I'm on and it's working for me. So, I wouldn't switch it now to go to something that I'm unsure of. (Woman, 55 years old) People of certain racial minorities have community histories of not being treated fairly by the healthcare system. And I think about like the syphilis studies that were done of black men, not recently but in the forties or something. And people were infected with syphilis and, then, not treated for it. So that would cause people in those communities to feel very untrusting of research institutions that might do that kind of things again. (Woman, 67 years old)
Social/Professional Role and Identity	Not identifying with the research matter	[If it is a research] that just does not relate to me or my lifestyle, I won't involve myself. I'm not going to involve myself in a transgender thing. I understand, I accept people for what they are, but it doesn't concern me. I won't involve myself with something that I really have nothing to do with as a person. (Woman, 64 years old)
Social influences	Perceiving researchers as self-interested	[I'm hesitant to participate] in research that is not clear in its objectives. It's one thing to have a study that is independent with a scientific frame. But a research done by a company that wants to try something […], I will have doubts. (Man, 69 years old) [I'm less willing to participate] if they don't have money from credible sources, or if they don't have an appreciation for community involvement in the project. (Woman, 67 years old)
	Having family members who ignore who ignore one's position regarding organ donation	My family is not aware of my condition, so it's difficult to approach them, to talk about it with them. I don't know if it will happen one day. Maybe my family sees death in a way different from mine. They could complicate things at the last minute. (Man, 65 years old)
Beliefs about Consequences	Perceiving risks for privacy	If I felt there was a risk, that my personal information wouldn't be kept confidential. Like if it got it to, for loss of a better word, the wrong hands. I think that's the one … Well, that and if this study was already underway and it didn't look promising, you know. (Man, 70 years old)
	Preferring to avoid interfering with medication	I do not want to take chances. My tritherapy functions, but if [I stop] and HIV bounces back. Let's say I do not want to play with this. (Man, 69 years old) [The thing that complicates this] is my cancer treatment. There might be a few [procedures] I'm not allowed to. For example, my dentist wanted to put a crown on some teeth but I can't do any surgery like that. (Man, 73 years old)
	Perceiving interferences between research and one's religious/cultural beliefs and rituals	People don't like to think of their physical being cut up or deteriorating. People have this idea that they're going to die and that some part of their being that they call their soul is going to go on to another dimension and that leaving the physical body intact is the best way to ensure whatever that has to happen. (Man, 70 years old) I think it's primarily religious bias. There are a lot of religion where after-eath research or end-of-life research would interfere with the end-of-life or after-death rituals that the person's family or community want for them. (Man, 70 years old) Some African women whom I know are focused on, if they die, their body has to go back to Africa … I think that people like that would not want a body to have an autopsy if it means they return a body in pieces back to Africa. (Woman, 67 years old)
Beliefs about Capabilities	Perceiving research procedures as complicated or time-consuming	I don't live in [the city]. If I need to go to [the city], it's a problem. It's an hour and a half, sometimes more, so it means 3 or four hours on the road, if I'm lucky. I would not want to do it. (Man, 65 years old) If the research was somehow very onerous, labour-intensive, was very painful, you know I might be very reluctant to [participant in a study]. (Man, 70 years old)
	Being concerned about one's post-mortem control over their body	I am ready to give things while I'm alive. The reason why not after my death is that, at some point, is that I want to give my body to science, but what if I die suddenly. It's a question of control: I want to have control on this. I made funeral arrangements. When I die, I want to be incinerated, I want to be placed in a mausoleum with my partner. I'm happy, it comforts me, I'm in peace. But if you want to take a piece of skin, hair, or a biopsy while i'm still living, I'm ready. (Man, 64 years old) And then, I can see that some people might worry about how it is it going to be used once they're gone. The control of what things are used for is a concern for some people. Will it be used ethically? I can see people having doubts about that. (Man, 77 years old)

In the environmental context and resources domain, one barrier was identified, Perceiving research as potentially risky or painful. Some participants mentioned how research and clinical studies could be associated with physical pain or forms of social suffering experienced by marginalized communities, making them hesitant or cautious concerning research.

For social/professional role and identity, we identified one barrier, Lack of interest in or identification with the research matter. A few participants suggested that they could be less willing to participate in a study that did not emphasize a theme important to them or focused on a group with which they did not identify.

In terms of social influences, we identified two barriers, including: Perceiving researchers as self-interested and Having family members who ignore one's position regarding organ donation. In the former situation, participants were hesitant to participate if research objectives were unclear, did not emphasize collective interests, or seemed profit-oriented. In the latter situation, participants mentioned that family members who ignored that one wanted to donate tissues or organs could also hamper participation.

With regards to beliefs about consequences, participants mentioned Perceiving risks for privacy: Participants were concerned that their personal information or HIV status could be disclosed or shared, in particular to family members. They also mentioned Perceiving interferences between research and one's religious/cultural beliefs and rituals, inferring that certain religious or cultural groups' beliefs and rituals may conflict with end-of-life research, especially when involving HIV biobanking and research autopsy, or require accommodations.

In terms of beliefs about capabilities, our analysis identified Perceiving research procedures as complicated or tedious and Being concerned about one's control over their body as barriers. Participants hesitated to participate in research requiring too many commutes to the hospital, and long or complex procedures, which could be time-consuming and reduce their quality of life. Further, participants feared that certain procedures involving HIV biobanking and research autopsy could interfere with their wills, or that their body could be mistreated.

Facilitators of participation

Table 5 also presents illustrative quotes for facilitators to willingness to participate in end-of-life HIV cure research, which were distributed across three TDF domains—social/professional role and identity, social influences, and beliefs about consequences—encompassing seven themes.

Table 5.

Illustrative Quotes to Facilitators to Participation in End-of-Life HIV Cure Research

Theoretical domain	Facilitator	Illustrative quotes
Social/Professional Role and Identity	Identifying with or being interested in the research topic	The topic, the subject matter, and the expectation that it would help answer things for different people [makes me more willing to participate in a study]. (Woman, 64 years old) If it was something that resonated with me, for my own interest. Then I would want to participate. (Man, 77 years old)
	Having worked in the health care system	Participating in research was in my culture, since I was a nurse. I know the importance of research. (Man, 69 years old)
Social influences	Knowing that the community or an ethics board approved research	[When I consider participation in a study], I want to make sure that there are community members in the research committees, and community consultations ub the research process. (Woman, 67 years old) [The main factor that I consider with research] is that it is ethically sound, that it has gone through an ethic's review. (Man, 77 years old)
	Receiving information from trusted, informed, and unbiased professionals	Having the medical team, researchers, and members of associations, and the person's family [really helps to participate]. They all sit together and discuss the topic tactfully with the person and its close ones. (Man, 71 years old)
Beliefs about Consequences	Perceiving research procedures as informative, safe, and clear	If there was a treatment and they want people to test, I would gladly volunteer with the understanding that the treatment may not work, but it won't make me sicker. It won't make my HIV worse. It may not make it better, it may not cure it, but it's not going make me worse off. (Man, 70 years old) For me to be relaxed and comfortable about [research], I would need a good understanding: how it works, how it's done, what is retrieved. (Woman, 64 years old) [I'm interested for research] like one, that was not necessarily medical. It was about the cardio-respiratory aspect of sports. They asked to ride a bike for X minutes, and then to run, and then we rode a bike or jumped. Each exercise was evaluated and they gave us their calculations about respiration, pulse, and pressure. (Man, 69 years old)
	Perceiving research as a last resort	[Willingness to participate in research] depends. When you are dealing with a severe problem like mine, I had blood clots every three months. I had 19 angioplasties. So I was: ‘What do I do? Could I try something new?’ (Man, 65 years old) If my medication, which works now, stopped working. Then that might be a whole different thing, right? Then if it becomes like: “Ok, we have something for you. It's experimental and we think it's going to work for you.” Then that's a different story. It changes everything. (Woman, 55 years old)
	Trusting that the body will be treated respectfully	[I would be willing to participate] because I just assume that there would be some respect given to the deceased body. (Man, 73 years old) [What I think is really important is] to have a respect for the corpse. You know, not to be, you know, abused in any way. (Man, 71 years old)

For social/professional role and identity, facilitators included Identifying with or being interested in the research topic and Having worked in the health care system or research. Several participants suggested that they were more willing to participate in studies emphasizing a theme important to them or focused on a group with which they identified. A few participants mentioned that professional experience as health care professionals or collaborators in research projects made them more willing to participate in research.

In terms of social influences, our analysis identified Knowing that a project is approved by the community or an ethics board and Receiving information from trusted, informed, and unbiased professionals as facilitators. Participants commented that approval by an ethics board or the inclusion of community representatives or people responsible for the implementation of respectful and ethical manners in research made them more likely to participate. They also highlighted that being able to discuss with several knowledgeable professionals (e.g., health care professionals, researchers, and community representatives) increased their comfort with research. Some participants also wanted to include family members in discussions, in particular to address post-mortem HIV biobanking and research autopsy procedures.

In terms of beliefs about consequences, facilitators identified included Perceiving research procedures as informative, safe, simple, and clear. Participants felt more drawn to participate in research with simpler, low-risk, and less time-consuming procedures, especially if they could learn something new about HIV, ART, or their health. Another facilitator was Perceiving research as a last resort. Participants suggested that, as their quality of life declined, had to endure heavy symptoms, or received unfavorable prognosis regarding their health, they could be more willing to participate in research for the purpose of alleviating suffering, or to consent to more invasive or risky procedures (i.e., try a new treatment) that they would not accept at the moment, especially if research could give them access to breakthrough or last chance treatments, or further testing that they could not access in other ways.

The final facilitator to participation included Trusting that the body will be treated respectfully, which was specific to research autopsy. For participants, believing that individuals' bodies would be treated respectfully during the process was reassuring.

Needs for information

Our analysis identified needs for four types of information, shown in Table 6. First, participants wanted to know about Objectives and procedures. Participants wanted to know the purpose and aim of studies, steps involved in participation, and particular details (e.g., who would take these steps, where, and how) about procedures toward and after the end of life. For HIV biobanking, they wondered where the body samples would be stored. Second, participants wanted to know about Risks involved in participation, in particular those for side effects of medication or interventions included in research.

Table 6.

Illustrative Quotes to Needs for Information About End-of-Life HIV Cure Research

Theme	Illustrative quotes
Objectives and procedures	[I would ask] where would this [study] be conducted? What procedures would be taken? What would be done while still living? What would be done after living? What procedures or steps would be taken if I am at the end and near the end-of-life? Would I be left to suffer, or would steps be taken to assist me medically? (Woman, 64 years old) I would want to know the mechanics of [the study], the nuts of bolts of it. How does it work? What's the research about? And what do I need to do? Obviously, I'm very supportive of the idea, so I would need very specific information about what I need to do to get everything ready so that I can participate after I'm dead. (Man, 70 years old) I would ask: “What's the goal?” (Man, 64 years old)
Risks	I would ask the question: are there side effects? (Man, 69 years old) I would want to know what are the risks. That's what I would like to know. (Man, 64 years old)
Possible accommodations with one's last wills or advance directives	Because I would want to make sure that after my death, I go to the crematorium and then go join my partner. There is also a notion of timing, because if they answer that all this will happen, you will be incinerated, you will be with him, all this, that's ok. But if it takes three months? I want to know. (Man, 64 years old) I would ask: “What's happening with your will?.” So there needs to be a kind of a care process taking it this into account as the research goes ahead. (Man, 77 years old)
Interests supporting or funding research	I would like to know which system is hosting the biobank. Is it a private sector or is it an academic sector? I would be more concerned if it was a private sector than academic. And yeah, so it's the integrity of respecting the intentions of the research and that that doesn't get transgressed. (Man, 77 years old) Who would be doing the research? Which companies? Who are they? That type of thing. Like I'm not sure who even does that. So, even now, I just don't know. (Woman, 55 years old)

Some participants also wanted to know about Possible accommodations with one's last wills or advance directives. Some participants mentioned that they had almost or already finalized their last wills and mentioned wanting to know whether potential end-of-life study procedures would be compatible with or adjustable to these wills before consenting to participate. Finally, participants wanted to know about Interests supporting or funding research. Knowing more about research sponsors (e.g., private vs. public sector, community-based organization vs. private company) and any potential conflicts of interest involving research stakeholders would help them assess the integrity and validity of a given study.

Discussion

Based on mixed quantitative and qualitative methods, this unique study with 37 older Canadians with HIV explores the factors affecting willingness to participate in end-of-life HIV cure research, in particular studies involving HIV biobanking and research autopsies. More than 75% of participants indicated that they would be willing to participate in a medical study toward the end of life, HIV biobanking, and a research autopsy to advance HIV cure research. These results reflect opinions about hypothetical studies and might not reflect actual behavior.

However, a study comparing hypothetical and factual willingness in six countries found that in about half of the studies, factual willingness was greater than hypothetical.²⁵ Participants mainly associated participation in HIV cure research with altruistic benefits, which coincides with similar studies conducted on this theme,^19,24,25 studies on the theme of participation in HIV clinical studies in general,²⁶ and our qualitative results on perceptions of research as a contribution to science and health, and a potential gift to community and younger generations.

Our results align with those of other studies on willingness to participate in biobanking.^27–31 The fact that participants perceived research as an Opportunity to learn more but were less willing to participate if they did not identify with the research matter resonates with a studies highlighting preferences for participation in personalized health research projects²⁸ and projects where research results were returned to participants, and that correlated unspecified research with unwillingness to participate in biobanking.²⁷

Further, as shown in other studies,^29,30 trust is important to recruit and retain participants, which explains participants' need for information about interests supporting or funding research and whether the community or an ethics board is involved, and may refuse to participate if researchers are perceived as self-interested. Finally, our results indicate important preferences for decision making about participation integrated with medical care, which has been documented,³¹ but also with one's wills-writing process, social life, and community.

Participants still expressed concerns. A few were willing to risk shortening their life expectancy, a result that differs from findings of a similar study conducted in the United States,²⁴ whereas their reluctance to experiment with physical pain and side effects concur with the latter. Participants also expressed reluctance in joining research with time-consuming or overly complex procedures. The importance of these concerns may be explained by most participants (n = 29/37, 78.4%) reporting a good or excellent quality of life. Moreover, results on perceived added meaning to one's life were also rather low, suggesting that participants already considered their lives to be meaningful.

Several participants mentioned that they could eventually consider research as a last resort, making them willing to participate to alleviate suffering, gain time, or try “last-ditch” interventions. This coincides with published evidence on people becoming more willing to participate in research as they become or perceive themselves as sick.¹⁹ Unfortunately, HIV cure research is unlikely to provide any direct benefits to older PWHIV.³² Information should be given to address unrealistic expectations.

Our results highlight a need for tailored recruitment strategies and information that integrates relevant values and/or highlight benefits for society and science, which generally coincides with recommendations found in the literature.^25,27–29 Results on willingness to participate and perceived benefits were slightly higher for participation in research toward the end of life than they were for the two other types of research. Our qualitative results reveal participants perceived HIV biobanking and research autopsy as potentially complex, painful, or risky procedures, with heightened risks of HIV status disclosure.

Moreover, HIV biobanking suggests long-term storage for “future,” unforeseen research with multiple risks of misuse and contingent perceived vulnerability for participants. Findings concerning the social and professional role and identity domain reveal a need to be included in interesting or relatable research. Barriers in the beliefs about consequences and about capabilities indicate concerns about risks for privacy and mistreatment of one's body that, with HIV biobanking, may remain as long as tissues and organs are stored, which make participants feel less in control.

Information to potential participants must be tailored to their current health and social or family situation, and potential changes foreseeable in the short and long term. Qualitative findings in the social influences domain emphasize needs for reliable and informed stakeholders prioritizing their interests that ought to shape information dissemination, and multidisciplinary dialogues involving community members are crucial, and have been emphasized in the literature.²⁰ Along this line, CanCURE includes multidisciplinary scientists, researchers, and students, in addition to the CAB, collaborating to produce lay language material, reflect on ethics of projects, and reinforce sensitivity.³³

Some participants would like their family and close ones to be involved, whereas others expressed concerns for their privacy. Also, concerns associated with religious beliefs or cultural rituals, and for one's last wills also suggest that information delivery may be constructed as two-way dialogues embedded and valorized throughout the enrollment and informed consent process.

Our study has strengths and limitations. Strengths include the fact that it fills a critical knowledge gap in the literature. Also, community members were involved in the study design and interpretation of results. We used mixed methods, and qualitative data saturated, enabling the elaboration of concepts to provide a richer understanding of participant beliefs. The study also employed broad inclusion criteria and allowed for the enrolment of PWHIV from across Canada. Further, adapting instruments already in use by the Last Gift study team in the United States, we were able to compare our results from PWHIV in Canada with PWHIV in the United States.^34,35

We must acknowledge important study limitations. Given the small sample, we did not perform statistical testing. We initially aimed at recruiting people 65 years of age and older; due to COVID-19 pandemic-related restrictions, we resorted to telephone and videoconference interviews. As many older individuals are less comfortable with technology, we ultimately lowered the minimum age of inclusion to 55 years old.

As with many research studies involving PWHIV, we faced challenges in recruiting equal numbers of men and women, in addition to participants born outside of Canada, Black, or Hispanic. For example, five participants were women (13.5%) and one participant identified as Indigenous (3.5%), whereas these groups represent, respectively, 23.4% and 10.0% of PWHIV in Canada.³⁶ Therefore, the findings of our study may not be generalizable to all PWHIV in Canada.

Data collection instruments were based on conceptual distinctions between three types of research, which, in practice, are not actually mutually exclusive: HIV cure research toward end of life can include a research autopsy, and HIV biobanking can include procedures pertaining to the two other types of research. However, data collection instruments thus included simple definitions of concepts inquired and open-ended questions about participants' understandings, which served to deepen our data and calibrate participants' understanding.

Also, only one investigator performed the analysis of qualitative data, consistent with this being an exploratory study. Finally, it is possible that the COVID-19 pandemic made people realize their own vulnerability and risk of impending death, which may have influenced responses in ways that are difficult to capture.

Still, our findings contribute toward understanding PWHIV's motivation and perceptions toward end-of-life HIV cure research and specifically with regards to HIV biobanking and research autopsy. For these novel research paradigms to be successfully implemented, it will be paramount to overcome the challenges identified therein. Ongoing dialogue and meaningful engagement between community members, researchers, and other stakeholders will be essential.

Authors' Contributions

The study idea was conceived by C.T.C. D.L., M.B., P.K., and B.L. contributed to the study design, with significant input from the CanCURE CAB (S.M., R.R., R.M., D.T., J.S., and J.T.). The CanCURE CAB, E.B., C.K., J.B.A.,, and J.-P.R. contributed to participant recruitment. D.L., and M.B. conducted the interviews. D.L., M.D., and L.S. designed and performed the statistical analyses. D.L. and C.T.C. interpreted the data along with input from all co-authors. D.L. and C.T.C. drafted the paper, with significant input from K.D. All authors have read and approved of the final article.

Author Disclosure Statement

None of the authors have any conflicts of interest to declare related to this study.

Funding Information

The authors thank the Réseau SIDA et Maladies Infectieuses du Fonds de recherche de Santé-Québec (FRQ-S) for funding this study. J.-P.R. holds a Lowenstein Chair in Hematology. B.L. is supported by a career award LE 250 from the Quebec's Ministry of Health for researchers in Family Medicine and holds a Canadian Institutes for Health Research Strategy for Patient Oriented Research (SPOR) Mentorship Chair in Innovative Clinical Trials. C.T.C. is supported by an FRQS Junior 2 career award.

Supplementary Material

Supplementary Data