Ethical considerations for engaging youth living with HIV in research: perspectives from youth, their caregivers and subject matter experts in Kenya

Abstract

Introduction:

Engaging youth living with HIV (YLWH) in research is critical to improving HIV-related outcomes, but their involvement raises unaddressed bioethical questions.

Methods:

This study used qualitative inquiry with Kenyan YLWH, caregivers, and subject matter experts (SMEs) to evaluate ethical considerations and strategies for research involving YLWH.

Results:

Interviews were conducted with 99 participants: 40 YLWH (median age 17.5, 50% female), 20 caregivers (70% female), and 39 SMEs (44% female). All participant groups discussed the need for HIV disclosure status assessment, confidentiality, and engagement of caregivers. Youth participants discussed the importance of clear protocol explanations and developing good rapport. All participant groups perceived youth under 18 to be harder to recruit due to a number of identified barriers. Clinic settings were the most acceptable place for recruitment.

Conclusion:

Participants provided perspectives on engaging YLWH in research that can be incorporated into protocols and regulatory guidelines.

INTRODUCTION

Children and adolescents (youth) living with HIV (YLWH) are highly vulnerable to HIV-related morbidity and mortality; HIV remains a top cause of death for YLWH globally, particularly in African countries, where the majority of YLWH live (UNAIDS, 2016). YLWH have worse clinical outcomes compared to younger children and adults, (Agwu & Fairlie, 2013; Nachega et al., 2009) and are at high risk for HIV drug resistance, especially those infected perinatally (Muri et al., 2017; Salou et al., 2016). Additional research with YLWH is critical to reducing morbidity and mortality and improving health equity for this population. Due to the vulnerability of this population, YLWH require additional ethical considerations and protections when engaging in the research process.

Living in poverty adds another layer of potential vulnerability for YLWH. Previous research has shown that people living with HIV (PLWH) are often significantly impoverished by the realities of HIV infection, including unemployment, lost wages, and high health care costs (Beaulière et al., 2010; Kumarasamy et al., 2007). Many households with a family member living with HIV struggle financially (Russell, 2004), highlighting the need to consider financial circumstances in the development of ethical research processes and protocols. Financial instability may influence an individual’s’ ability to engage in research procedures and incentives or compensation for time may influence participation decision making.

HIV-related stigma and discrimination increase the risks and vulnerabilities experienced by PLWH and must be considered when engaging YLWH in research. Previous studies have demonstrated that perceived stigma is associated with delayed initiation and presentation to HIV care, poor antiretroviral treatment (ART) adherence and long-term retention in care, and negative impacts to interpersonal relationships (Sayles et al., 2009; Katz et al., 2013). As such, researchers should consider the ways in which HIV-related stigma impacts how and where to engage YLWH, as well as additional protections that need to be in place as part of research studies for this vulnerable group.

Despite the unique needs and considerations for engaging YLWH in research, there is a paucity of bioethical conceptual and empirical work on the vulnerability of YLWH and how best to engage them in research (Bracken-Roche et al., 2017; Lange et al., 2013). Adolescence includes a broad developmental spectrum over the period of 10–24 years (World Health Organization, 2019), with shifting social and legal autonomy, and requires age- and culturally appropriate engagement in research (Bekker et al., 2014; Zulu et al., 2018). Guidelines call for assent from minors under the age of 18 years and consent by a parent or guardian (Cheah & Parker, 2014; Kelley et al., 2016), but the prescribed ages at which to begin obtaining assent vary from one setting to another (Vreeman et al., 2009). Other considerations such as disclosure of HIV status within research processes may infringe on YLWH’s rights to privacy and dignity (Folayan et al., 2014; Singh et. al 2006) and increase risks for HIV-related stigma, discrimination, and violence (Baumgartner et al., 2014; Wolf et al., 2014).

The Kenyan National Research Ethics Guidelines (Republic of Kenya, 2004) highlight the components and requirements for informed consent, ensuring participant privacy and confidentiality, and additional protections for vulnerable populations. This is in line with the International CIOMS 2016 guidelines (Bandewar, 2016), that provide additional context on study risk-benefit determination and ensuring adequate comprehension of consent prior to enrollment, but gaps remain in ethical engagement of YLWH. There are limited guidelines and policies that address the ethical issues for research with YLWH in diverse settings Mark et al., 2018; Armstrong et al., 2018). Furthermore, there is limited research on the perspectives of YLWH themselves, their caregivers and subject matter experts in low- and middle-income settings that can be used to inform policies guiding ethical research engagement with this population.

While there is an urgent need to increase YLWH’s participation in research, there remains a gap in understanding of the bioethical considerations for engaging this vulnerable population in the process. The objective of this study was to identify and explore the bioethical considerations for engaging YLWH in research from the perspectives of YLWH, their caregivers and subject matter experts in Kenya.

METHODS

Study Setting

This study was conducted in Kenya at AMPATH (Academic Model Providing Access to Healthcare) (Einterz et al., 2007), a long-standing partnership between a consortium of North American and Kenyan academic medical centers in partnership with the Kenyan Ministry of Health that provides comprehensive care for over 160,000 Kenyan people living with HIV, including over 6,000 youth (AMPATH, 2014). This study was nested within a longitudinal cohort of YLWH assembled in 2010–2013 who participated in several clinical studies to investigate ART adherence and drug resistance. Eligibility for the original parent study was: 1) perinatal HIV infection, 2) ≤14 years of age at enrollment, 3) on 1^st-line NNRTI-based ART regimens, 4) receiving HIV care at an AMPATH clinic.

Study Design

Semi-structured interviews were conducted with three categories of participants: 1) YLWH enrolled in the parent studies, 2) caregivers of YLWH enrolled in the parent studies and also enrolled in this study, 3) YLWH who have not participated in research and could therefore provide unbiased input, and 4) subject matter experts, including healthcare providers, researchers, community leaders, and regulatory and bioethics experts. As participants enrolled in the parent study have several years of experience working with our research team and may have biases toward the processes used historically, we enrolled a cohort of adolescents without research experience to provide an additional, unbiased perspective on these questions.

Sampling and Recruitment

a. YLWH enrolled in the parent study

Random sampling was used to enroll YLWH participants from the parent study and were included only if they were (1) between 10 and 24 years of age, (2) aware of their HIV status. Participants with upcoming routine clinical visits were approached at the clinic; other participants were contacted by phone. No contacted participants refused participation in this study.

b. Caregivers of YLWH enrolled in the parent study

Caregivers were similarly recruited through random sampling from scheduled visits. Caregivers were defined as someone who was already knowledgeable about the health status of the YLWH, including their HIV status, and was involved in the care, well-being and health decision making of the youth participant. Participants were eligible if they were (1) a caregiver of a YLWH enrolled in the parent and current study, (2) 18 years of age or older, (3) aware of the HIV status of the YLWH, and (4) knowledgeable about the care and research participation of the YLWH enrolled in both the parent and current study. Caregivers were approached at the time of the participants’ routine clinical visit or by phone.

c. YLWH with no history of research participation:

Participants were randomly sampled from clinical appointments at the Rafiki Center of Excellence for Adolescent Health, a comprehensive adolescent health clinic providing HIV services, which also serves as a major recruitment site for research studies with YLWH at AMPATH. Youth were eligible if they (1) were between 10 and 24 years of age, (2) living with HIV and aware of their HIV status, (3) receive HIV care at the AMPATH/MTRH Rafiki Center of Excellence for Adolescent Health, and (4) self-reported not being previously involved in clinical research studies.

d. Subject matter experts:

Subject matter experts (SMEs) were identified by the research team and were eligible if they were: (1) 18 years of age or over, (2) a member of one of the following groups: community leaders (village elders and chiefs), members of an AMPATH community advisory boards, healthcare providers, members of Institutional Review Boards (IRBs) (both local and national), researchers from the AMPATH Research Network and other institutions conducting research with YLWH in Kenya, research laboratory leadership, and government or policy representatives. The laboratory experts included in this study provide expertise in laboratory processing and associated protocol development for studies involving vulnerable populations, and in many cases, they also conduct the phlebotomy directly with study participants. In addition, they participate in protocol development related to the storage of specimen and consideration of the potential future uses. AMPATH community advisory boards are comprised of members of the community who provide input and relay information on research and programmatic initiatives.

The only exclusion criteria for all participant groups were the inability to provide written informed consent to participate, or in the case of those under 18 years of age, the inability to provide assent themselves and consent by an appropriate caregiver. Participants from each group were enrolled in the study until thematic saturation was reached within each participant group.

The interview guide was informed by the study team’s long-standing experience enrolling YLWH in research and a literature review. The interviews covered two domains: (1) identifying, enrolling, and protecting YLWH in longitudinal clinical research, and (2) collecting, testing, biobanking, and sharing/future use of biological samples. Participants were asked to consider the processes for and protections needed to identify and enroll YLWH in research, including appropriate setting and methods for recruitment, personnel engaged in the research process and strategies for ensuring confidentiality. Additionally, participants were queried on the best strategies for collecting and storing samples, including the conditions for when a participant should be re-contacted for additional use of their samples, and the appropriate documentation for future use studies. This paper discusses broad ethical considerations for research with YLWH, including how research involvement changes from adolescence into adulthood; involvement of caregivers in research; and ethical considerations when engaging a population with low socioeconomic status and high orphanhood. Analyses of other domains will be described elsewhere.

Data collection and analysis

Interviews were conducted by two experienced Kenyan facilitators (one male, one female) in either Kiswahili or English, depending on the participant’s preference. Facilitators received training on the study protocol and in semi-structured interviewing techniques. The facilitators had no prior relationship with the study participants. Interviews with adolescents, caregivers and most of the SMEs were conducted in-person in a private room within the clinic setting. A minority of SME’s conducted interviews in their private offices; the IRB member participants conducted interviews in a private room over zoom. No observers were present during the interviews. Interviews were audio-recorded, transcribed, and interviews conducted in Kiswahili were translated into English for analysis. Deductive thematic analysis was led by two researchers (HK and EG) based on an initial coding framework derived from the interview questions and reviewed with JA and AC. The researchers independently extracted data using the qualitative software program NVivo, version 12 (NVivo, 2018). The same investigators (HK and EG) led inductive analysis, and extracted emerging themes independently before comparing results and reaching consensus on relevant themes. Data from the three participant groups were aggregated to identify themes applicable to all groups, followed by an exploratory between-group analysis of differences.

Ethical approvals

Additional approval was received from the National Commission for Science, Technology and Innovation (NACOSTI), a Kenyan government research regulatory body (reference number NACOSTI/HW/3/1/16). All participants over 18 years of age provided written informed consent to participate in study interviews, and participants below 18 provided written assent and caregiver consent. A detailed, standardized informed consent/assent form written in either Kiswahili or English was read aloud with adequate time for questions and clarifications, and written consent/assent was obtained by trained, bilingual research assistants with experience in recruiting YLWH in clinical research studies.

RESULTS

Participant Demographics

Semi-structured interviews were conducted with 99 participants (53% male): 40 YLWH (median age 17.5, (age 11–24 years, 50% female), 20 caregivers (70% female), and 39 SMEs (44% female, 45.9% community leaders, 25.6% health care providers, 15.4% clinical researchers, 7.7% social sciences researchers, 2.7% international research experts, 2.7% laboratory experts).

Issues to consider when engaging YLWH in research

All participant groups discussed issues and vulnerabilities to be considered when ethically engaging YLWH in research (Table I). All participant groups discussed the role of youth demographics and circumstances at the time of enrollment in the research study; youth age, disclosure status and education were cited as factors that may influence how youth engage in research. Youth privacy and the need to ensure confidentiality in the research process was identified as essential to research participation for YLWH by all groups, suggesting that researchers should de-identify participant data wherever possible. Youth comprehension of the research process was cited by all groups as well; during the enrollment process researchers need to thoroughly explain the purpose of the study at the level of the adolescent participant, what will be asked of youth, the risks and benefits of participation, and that participation is optional. Subject matter expert participants were the only group to express concern that youth may not know or feel like they can decline participation. Adolescent participants wanted researchers to better understand the experiences of YLWH, including the diversity of adolescent experiences based on age, living situations that may influence HIV-related behaviors, and the need for psychosocial support. All participant groups viewed family involvement and socio-economic status as factors that might influence youths’ ability to participate; the development of good rapport and a trusting relationship between researchers and participants/their families were recommended; these perspectives were held more commonly by adolescent and caregiver participants. All participants discussed the importance of obtaining consent from caregivers when working with YLWH under the age of 18 years. Compensation was viewed as but also as potentially coercive for youth and families experiencing financial instability.

Table I.

Issues to consider when engaging YLWH in research

Theme	Sub theme	Illustrative Quote
Adolescent life experiences	Age	‘Here we have [adolescents] 10–24… most of the time their age matters on how they are going to respond to the question you are asking them.’ – SME health care provider, female ‘First of all, they should consider the age, the sex and the maturity level and also the background of the participant.’ – above 18 female adolescent
	Disclosure status	‘The first thing that is important is ensuring, first of all, that these young people have already completed disclosure. I think that is the most important thing. Already disclosure has been done and they are already accepting their status. Once that is done, I think it will become easy to know take them through other studies.’ – SME health care provider, female
	Education	‘We also consider the level of education because also those who might not have schooled well might not be in a position to understand much about HIV/AIDS.’ – SME Chief, male
	Family involvement	‘Before he makes the decision to participate in the study, he should inform his/her caregiver to be aware that he/she is participating in certain research.’—caregiver, female
	Finances	‘Then source of income is how or what means they have that enable them to reach the facility. If you recruit these participants and they need to come back for revisits, how are they able to get sources of funding for their transport to and from?’ – SME health care provider, male
	Medication taking behaviors	‘About the time, where I live, my living situation—the doctor would like to know how I live because I might be coming for drugs, but I don’t take them.’ – below 19 male adolescent
Privacy considerations	Confidentiality	‘Some youths fail to participate because they fear that their information could leak to others. The researchers should keep the information confidential.’ -- caregiver, female ‘Majorly the idea of anonymity. Most people don’t like their status of them living with HIV been out there. Been able to keep that confidential and respecting their privacy is something that would be a huge deal.’ – above 18 female adolescent
	De-identify data	‘Maybe a doctor should just give them the information but not the identification of that person.’ – above 18, female adolescent ‘I think they should use code numbers more often, like when a certain research group wants to conduct research on a certain client, I think number should be used more often instead of going and checking the names and files of clients.’ – above 18 male adolescent
Participant comprehension	Research transparency	‘I would like them to explain how research is done. They should also tell the youth about the benefits of participating in such research. They should know that research mainly focuses on their health.’ – below 18 female adolescent ‘When a young person is participating in research he should be [told] the type of research that he is participating in. He should fully understand what is being done to him. You know sometimes you could be leading someone as though you are taking a cow to the slaughterhouse, he has no idea of what is supposed to happen. The researcher should ensure that the young person understands what the research is about, for example if it’s the blood… he should know what is being done to him.. you should be telling him that this is where it is taken, this is what happens—you know when he only sees that blood is collected.’ – caregiver, male
	Participation is optional	‘Being able to comprehend what consenting to research is, some of them think that they are obliged to consent. So just being able to assess their ability to consent.’—SME clinical researcher, female ‘It’s possible if you were not very keen to ensure that the adolescents clearly understand that this is research and it’s not compulsory. Especially if the person who is doing research is a senior, to them it feels like it is obligated, it is a must that you participate. Someone older than you is asking you to participate—you have power over them, and they don’t know that they don’t have to participate.’ —SME clinical researcher, female
	Study purpose	‘The most important point to consider is what you are going to do with these YPLWH in terms of -- are you either trying a drug, are you getting samples, the amount of sample -- and sometimes most YPLWH need to be much involved on what will happen to them. They need to understand very well what is being done.’ – SME health care provider, male
	Risks and benefits	‘I think first what we consider is what is the focus of the study… what is the level of risk in terms of participants engaging in the study, is it of high risk or is of low risk, what are the benefits and the ballot between the two?’ – SME, social sciences researcher, female
Incentives	Challenges with compensation	‘Most adolescents require maybe—okay they will only do research, if they can have something directly—maybe what’s in it for me if I participate in research? Most of them will want maybe—since you have already taken their time, the first question they will ask is whether they are being paid since that is what they say. Whether they are being paid, because I am giving my time, so if the adolescent hears that there are no incentives, they will keep off the study.’ – above 18 male adolescent ‘And then the other important question is the issue of coercion, especially because I know like most research would probably give some as compensation. And for adolescent any amount of money even 200 shillings might be a lot of money and so if this information is given beforehand, then it might be coerced because they are interested in that little money that will buy whatever, whether it’s a sweet or anything... And so without understanding whatever the research is, they might quickly just accept. Because they have some 500, 200 bob. That for them is a lot of money.’-- SME clinical researcher, female
Researcher responsibilities	Accept diverse views and opinions	‘I think they should understand that [because of my age] what I am saying is different from another person. The ideas are not the same.’ – above 18 female adolescent
	Provide psychosocial support	‘Support them. It is very hard for someone to come here and give their information, it is very hard. And it is very hard for someone to accept themselves, my request is that they work together with them, they understand the problem they pass through while using medicine.’ – above 18 female adolescent
	Develop a rapport with participants	‘You can form kind of a rapport; warm kind of vibe rather than being too direct with them. Being friendly and warm to them. When you are friendly to someone, they open up and more information is actually…said.’ – above 18 male adolescent
	Consent	‘Okay, the research party should seek consent from the caregiver. The consent is really a vital part because you cannot just take something and do whatever you want to.’ – above 18 male adolescent

Bioethical considerations for youth research engagement by age group; YLWH under 18 vs. over 18

Participants were asked to consider the differences in needs for youth under and over 18 years (Table II). All participant groups reported that youth under 18 may be unaware or less accepting of their HIV status, which may present challenges in participation in the research process. Younger youth may be shy and less communicative, especially in environments in which they feel uncomfortable, and may not understand research as well as older youth, requiring additional time and explanation from researchers. Caregivers shared that younger youth were more likely to accidentally disclose their status to others across all settings. Logistical challenges may arise engaging younger youth in research, especially because of reliance on their caregiver to provide consent and scheduling issues for those in boarding school. In contrast, youth over 18 were perceived by all groups to be more accepting of their HIV status, better able to understand research and more adherent to research procedures. All participants groups highlighted that youth over 18 have decision-making autonomy and are therefore able to provide consent for themselves and manage the logistical considerations for their own participation. There remain questions related to what age researchers may ethnically engage YLWH, and if disclosure screenings in the research process are sufficient in preventing accidental disclosure.

Table II.

Research considerations by age group

Theme	Subtheme	Illustrative quote
YLWH under 18	Acceptance of status	‘The young ones are still in denial. They are still not ready to say it out or are still questioning their parents why they did so and yet it’s not their parents it’s just something that happened and they have to accept it.’ – above 18, female adolescent
	Unaware of HIV status	‘It is harder for the younger ones because they do not even know their status. They will question why they are taking medicine and their peers are not. And the other children will also start asking why the child is taking medicine.’-- caregiver, female
	Accidental disclosure to others	‘As for the little ones, they are still young and they don’t know how to hide their secrets, they end up disclosing what is not supposed to be known.’—caregiver, female
	Limited understanding of research	‘I think the younger would probably not be able to understand and tell the benefits of a research study like the research study is being done for a better course.’ – above 18, male adolescent
	Challenges in recruitment and adhering to research	‘Children are usually late and also fail to take the full treatment while adults are always on time and always take the medication.’ – below 18, adolescent female ‘Most of these persons within that age group are either in school or have just completed school, so if you are recruiting participants within a school environment for example and boarding school for that matter, children who are boarding and do not have access to their parents that can be challenging in terms of recruiting the for the study because in addition to them saying yes to the study I also have to consent from their parents.’ – SME, IRB female
	Reliant on caregiver	‘If I was below 18, I think the matter will purely depend on them [caregivers], they will take full responsibility on making decision regarding me partaking in any research study in matters of giving out my blood or anything as in they would be fully taking a pride on it.’ – above 18, male adolescent ‘Unlike the adults over 18 years who can speak on their own behalf, adolescents younger than 18 means that I have to seek consent from them if they are emancipated or seek both consent from their guardians or their parents and seek assent in addition to that. That already poses logistical issues.’—SME IRB, female
	Shy and less communicative	‘In most cases, the group that is below 18 years—they tend to be less vocal therefore it is difficult to know whatever they are interested in or maybe there might be something that they are not comfortable with, but they can’t speak out because of fear compared to the other group who are maybe more mature, they know what they want and they will speak out whenever they feel something is not right.’ – above 18, male adolescent
YLWH over 18	Acceptance of status	‘For the older ones it is not hard because they are aware of what [HIV] is, let me take these medications… so that their body can be better, so that they can still do other things, so that even them one day they will be able to have their own family.’—caregiver, female
	Better able to understand research	‘They know themselves because after disclosure, they are able to understand themselves and understand why research is being done.’—caregiver, female
	Decision making autonomy and consent	‘On the 18 plus side, you can see that most of the people depend on themselves, they are independent, they have broken the leash from their parents so they can think rationally on issues that affect them daily and form solutions out of them.’ – above 18, male adolescent ‘For me, the main difference between the under 18 and over 18, is the fact that the over 18 can make their own informed decision on participation, meaning they can give their own informed consent because they are of age… and that goes now to the age at which we think they can be able to understand the whole consenting process before they decide to participate in a study.’ – SME, IRB female
	Easier to adhere to medication and take care of self	‘You know, those ones who are below 18 need assistance maybe from parents as far as medical issues are concerned. Those ones above [18] are responsible people. Whenever they have known that they have HIV, they will be in a position to take care of themselves. They should know when and how to go look for ARVs.’ – SME Chief, male

ARVs= antiretroviral medications

Strategies for ethical identification and engagement of YLWH in research

All participant groups provided recommendations for how to ethically identify YLWH eligible for participation in research (Table III). All participants recommended identifying youth through the clinical program, through support groups that involve youth, and through other PLWH. Participants had varying perspectives on recruiting using medical records; SME participants more commonly discussed the limitations of using medical records whereas caregivers viewed medical record review as appropriate and comprehensive. SMEs viewed consultation with the youth participants’ clinicians as a better, more ethical approach.

Table III.

Strategies for identifying and engaging YLWH in research

How to identify research participants	Medical records	‘Maybe going through medical records challenges might arise if the records are incomplete, either incomplete because you have YLWH getting lost to care or not honoring their appointments. Or they might just be incomplete because the people who are supposed to ensure that the records are well maintained don’t bother to fill it in. Going through medical records can have its own pros and cons.’ – SME health care provider, female Interviewer: So you are saying that it is okay to identify these youth by going through [medical] files. Participant: Yes Interviewer: You think it is the best? You are advising researchers to use that method? Participant: It is the best, it has the whole picture of who Marie* is. – caregiver, female
	Clinical care	‘You can trace them when they come for clinic.’—above 18 female adolescent ‘During their routine clinical care, that is the right way to approach’. – caregiver, male
	Support groups	‘For example, for this age group, you call a meeting for that age group—they have a group so you call them and let them know that they are treasured. You approach them in the group, when you approach them individually it will be different and you won’t understand them but if you get 10 at once who are in that age group, they can meet and talk to each other.’ – caregiver, male
	Other PLWH	‘What they can do is, first, for those who are here and infected, they should be united. They are the ones to bring those who are in hiding, out. You cannot go from here and start calling out publicly for those who have the disease. No one will come. They know how they are among themselves.’ – caregiver, male
Where to engage research participants	Clinical care	‘If they are HIV positive, and they have been recruited in the care program, then the care program should be where you should be able to get hold of them.’ – SME clinical researcher, male
	Research/clinical relationship	‘I think they can approach them through mentorship. Sometimes they come to the hospital and some of their colleagues who are more experienced can talk to them, they play and have fun with them, they drink tea—I think that is where they can recruit them.’—caregiver, female
	Face to face	‘Yes. I would not advise online. I would prefer face-to-face because I think it also gives young people time to process the information you are being asked for and to think about how to hand in over. I may also think the researcher would be in a position to see which young people to continue interviewing and which one to protect. Yes.’—SME international research expert, female
	Technology/social media	‘A WhatsApp group which these adolescents have…social media groups can also be used.’ – SME health care provider, male ‘They can open a WhatsApp group for those who have smartphones and maybe for those who come to the clinic—they have their numbers, they can send them a message and talk to them in the group about the importance of research and others will join and they will get youths easily.’ – above 18 male adolescent
	Social support groups	‘And again, another one, which might also be another avenue is if they have social support groups, where they meet and share their experiences, which is out of the care program that is, so that’s another place I see one can be able to get them.’ – SME IRB, female
	Through peers	‘Basically, I would say in matters of youth, it would be much more invited if a fellow youth would come to talk to you so I would say the research company should find the agents in terms of youths who understands the matter to a certain degree to be able to communicate the missing point or the people who do not know what is going on. It would be more productive that way.’ – above 18 male adolescent ‘There is only one way to bring them close, and this is by using those who are close to to reach them.’ – caregiver, male
	Social events	‘Youths like getting together, they like socializing, so if you bring them together, in that point they are their true selves, they can make their views clearer than other times.’ – above 18 male adolescent
	School	‘There are some schools which are accepting to all these groups of people and there are others whereby even the teachers stigmatize the students who are HIV positive. That would negatively affect the student if you maybe go and just start asking research subjects in a place like a school.’– above 18 male adolescent ‘In research concerning HIV, you cannot go to schools to get them because others will know and they will be stigmatized; I think clinics are the best place because information is kept confidential.’—caregiver, female
	Community health workers (CHWs)	Interviewer: What about using a community outreach worker to reach those to enroll in research? Respondent: That’s a good idea because health workers are the people who know those who are very sick [more so] than the researcher, so they could be of help. – SME community advisory board, male ‘Not many agree to that [CHW] because you want to have your privacy. For these community health workers you never know how they could see you and they are like ‘There she is coming, this person is always at this place she comes to participate in research.’ So it is just better when someone personally comes for their clinic because those are your own personal issues.’ – caregiver, female
	Home setting	‘At home it is like the family is staying together. No one wants their private matters exposed to the public’. – caregiver, female
	Church	‘No, churches are not a place to do research… Due to privacy. For example, if you speak with the pastor and he says that you can go ahead to do research, other people will want to know. When an announcement is made requiring those who are HIV positive in church, the youths will not take part because they do not want others to know.’ -- caregiver, female

^*Participant name has been changed.

Study participants also made suggestions for how to engage eligible youth in research. Recruiting youth through their involvement in the clinical care system, existing researcher/clinic relationships and support group settings were viewed as acceptable; using WhatsApp, other social media platforms and peers living with HIV were also viewed favorably by all groups. Recruitment from less private settings, including schools, community outreach, and the home setting, were viewed less favorably by all participant groups due to concerns around HIV-related stigma.

DISCUSSION

Participants in this qualitative study identified key vulnerabilities to consider for ethical engagement of YLWH in research in our setting in western Kenya, including HIV disclosure status, socioeconomic status, HIV-related stigma, and age-related differences in life experience and education, among others. Additionally, all participants described potential strategies to address these vulnerabilities and minimize associated risks and burdens to youth research participants. The perspectives of participants in this study in some cases focused more on the feasibility and logistical considerations for engaging YLWH in research. For some themes, participants did not delve into the ethical issues involved, perhaps reflecting a lack of consideration of or knowledge about these ethical challenges.

All participant groups discussed the need to consider youths’ socioeconomic circumstances and the costs associated with participation as a pillar of ethical engagement in research. Some SME participants described how families might experience unfair economic and financial burdens when engaging in research. Adolescent and caregiver participants perceived the financial burdens of research participation to be especially burdensome when younger youth participate in research, as they require a caregiver to travel with them to provide informed consent, and time spent traveling and engaging in the research study represents time away from work, lost wages, and direct costs of transportation. Previous work in Kenya to explore perceptions of the important boundaries for payments and participation in research highlighted concerns with accounting for costs associated with unpaid work and lost income arising from time spent in the research program (Njue et al., 2014). Participants noted that direct costs, like funds spent on transport were easy to account for, but duration of time required for participation was less clear (Njue et al., 2014). Shorter periods of time were seen as less in need of compensation because they would be less likely to incur significant economic costs; for periods of 3 hours of more, compensation was viewed as important (Njue et al., 2014).

Adolescent and SME participants also cited that another component of offering an ethical level of compensation was the need to ensure that compensation for participation in research studies was not so high as to be coercive in environments or participant groups with high levels of financial insecurity. Many studies have investigated the role and impact of financial compensation for participation in research and have concluded that they affirm participants’ value and importance of their participation by treating them justly and with respect; compensation acknowledges the effort given to participate (Grant & Sugarman, 2004). Determination of appropriate financial compensation for research participation is a challenge. Researchers must consider a balance between coercive payments and under-paying of participants, as under-payments remain a challenge for vulnerable populations that experience increased burdens related to the financial costs of participation. Using financial compensation may become unethical when combined with other factors, including when the risks of the study are high, where the participant is dependent on a relationship with the researcher or when the incentive is inappropriately large (Grant & Sugarman, 2004). This is especially the case for vulnerable populations, like PLWH who may experience significant financial instability. It is assumed that compensating study volunteers in proportion to the service they offer is ethical due to the fact that the compensation of benefit remuneration model is assumed to encourage voluntary and altruistic participation in research. These strategies allow for withdrawal from research participation, regardless of the reason. Institutional review boards should set standards for research compensation with consideration for the setting in which research is conducted to avoid coercion.

All participant groups stressed the importance of better explaining research procedures to youth enrolling in research; youth and caregiver participants had a desire to be better informed about study procedures and recommend use of age-appropriate information. Young children have demonstrated the capacity to comprehend basic parts of research, albeit with varying level of understanding; trust in the research team was identified as a critical factor in study engagement decisions and risk evaluations (Ahad & Lim, 2014). Previous studies have evaluated youth understanding of research concepts, and found that complex research concepts were consistently understood by youth when the information was provided at the child’s developmental level (Weithorn & Campbell, 2017; Burke et al., 2005). Weithorn and colleagues also found that at 14 years, children demonstrated a competency level equivalent to that of adults (Weithorn & Campbell, 2017). Cleary and colleagues demonstrated that most adolescents at high risk for HIV infection demonstrated key abilities to make meaningful decisions regarding participation in a HIV vaccine clinical trial; their findings were comparable to those among the adult population (Cleary & Walter, 2010). These data support the perspectives of our participants that youth are able to understand complex research concepts and there is a need for researchers to ensure consent processes and other study procedures are communicated in age-appropriate ways.

All participants discussed the different research considerations when engaging youth under and over 18 years. Due to policies that require researchers to obtain consent from a caregiver for youth under 18 years, this group was considered by all participant groups to be more challenging to engage than those over 18, who are able to provide consent and make decisions on their own. Additionally, youth under 18 are less likely than their older counterparts to be HIV-disclosed or accepting of their status, which may impact research engagement. As such, youth over 18 were perceived by all participant groups to be more capable of adhering to medication-taking behaviors and research procedures. Nonetheless, the participation of youth under 18 years, though requiring additional ethical consideration, is still necessary to guide interventions and clinical care for this vulnerable group. Caregiver involvement in HIV-related research requires additional ethical considerations and protections, particularly for sexual and gender minority youth, emancipated minors and those whose who have not disclosed their HIV diagnosis to others. In these cases, waivers of parental consent for participation in research may be granted. Researchers may consider relationship development with participants an integral part of ethical recruitment for this key group, in order to identify appropriate caregiver role and additional protections needed for engagement.

Most study participants, from all groups, discussed stigma-related challenges related to recruitment and enrollment of YLWH in the home, school and community environments and the critical need for privacy and confidentiality in the research process. Interestingly, while SME and caregiver participants viewed identification of eligible participants through medical records positively, youth participants shared concerns regarding possible breach of confidentiality and others finding out about their HIV status. This finding highlights discordance in youth-caregiver perspectives on research participation and the need to incorporate youth in the research development process, especially as they begin to have autonomy over their health care and engagement with the health system. Considering youth perspectives, particularly as it relates to their privacy and engagement in research, is critical in designing programs and interventions for their benefit. Clinician researchers, who both provide care for YLWH and conduct studies to support them, may be well positioned to support the identification and enrollment of this highly-stigmatized, vulnerable group. Previous studies have cited experiences of enacted and anticipated stigma in these settings, in the forms of interpersonal discrimination, bullying, social isolation and vengeful disclosure (Mutumba et al., 2015; Abubakar et al., 2016). In the home, YLWH are vulnerable to power imbalances caused by dependency on their caregiver, especially among orphans who may not be able to challenge harmful dynamics (Crivello & Chuta, 2012). These dynamics influence the ability to recruit youth in home settings, may limit the ability to obtain caregiver consent for youth under 18, and may impact mental health and medication-taking behaviors in this setting. These data reinforce the need to carefully consider the locations and methods by which we engage YLWH in research studies, so as not to contribute to the stigmatizing experiences of this group. Previous work in this setting to develop a teacher training module to reduce HIV-stigma in the classroom supports our findings; education sector SMEs and YLWH reported significant experiences of discrimination in the school setting, both from teachers and peers, but also from the school sexual health curriculum (Chory et al., 2021). Finally, participants recommended engagement with YLWH through peers and leveraging peer social interactions, a strategy with demonstrated success in this setting (Shah et al., 2018; Ott et al., 2020).

Participants from all groups recommended using social media or other mobile health strategies for ethical recruitment and enrollment of YLWH. Despite growing interest in the use of mobile health strategies for research recruitment, there are currently no regulatory guidelines and limited resources for institutional review boards and investigators to navigate this approach (Adair, 2015; Gelinas et al., 2017). Recruitment and participation through mobile health strategies have many potential benefits, including reducing power differentials between adult researchers and youth (Rao et al., 2018; Fox et al., 2007), facilitation of open communication due to a decreased perception of judgement (Rao et al., 2018; Cleary & Walter, 2010) and better retention due to increased cell phone ownership and ease of use (Rao et al., 2018; Cleary & Walter, 2010). Additionally, mobile health strategies address distance and transportation barriers that may affect harder-to-reach populations; for YLWH, mobile health can offer benefits such as anonymity in settings with high levels of stigma (Rao et al., 2018). Importantly, mobile health strategies may not be effective in reaching communities with significant financial insecurity.

LIMITATIONS

There are several limitations to this study. First, while the overall study sample size was adequate, participants belonged to four key groups; sub-group sample sizes were small, which may limit generalizability. Second, while many of the resulting themes are applicable to all youth living with HIV, the interview guide probed experiences related to youth perinatally infected with HIV, which may also limit generalizability. Lastly, the perspectives gathered in this study are from a specific population in western Kenya and may not be generalizable to other regions of Africa or resource-limited countries.

CONCLUSION

Participants provided insightful considerations to guide the ethical engagement of YLWH in research, highlighting age-specific differences in participant needs and experiences, the ethical use of financial incentives for participation, and the need for confidentiality in the research process. Youth over 18 years were perceived as easier to engage in research due to their ability to provide informed consent and better understand their HIV status. HIV-related stigma remains a critical consideration in the engagement of YLWH in research, particularly in the context of how and where youth are recruited. Future research should investigate the bioethical considerations of using social media and mobile health strategies to recruit YLWH in research.

Best Practices:

This study discusses the broad ethical considerations when engaging YLWH in research, from the perspectives of youth themselves, their caregivers and subject matter experts. The inclusion of YLWH in HIV research is both ethically justified and necessary, considering their unique vulnerabilities in HIV treatment; these findings may be used by researchers and policy makers to inform ethical engagement of YLWH in the research process. Our data highlights the unique needs of YLWH both above and below consenting age, the pervasiveness of stigma and how it may impact the places and ways researchers interact with YLWH, and the responsibilities of investigators to consider the comprehensive needs of this vulnerable population.

Research Agenda:

There is limited data on how best to ethically engage YLWH in the research process from youth themselves; youth perspectives are critically needed to better understand their vulnerabilities and needs, and further refine guidelines to ensure adequate protection. While comprehensive ethical guidelines for engaging vulnerable populations exist, there remain gaps in addressing the nuances of the experiences of YLWH in low and middle income setting contexts. The data presented here provides insight into the concerns of youth, their caregivers and subject matter experts, including confidentiality concerns around accidental disclosure, risks of coercion through incentives, stigmatization in community settings and key developmental differences between youth above and below the consenting age, among others. These factors must be considered in the development of research protocols enrolling YLWH; continued investigation to understand how these perspectives can be operationalized is needed.

Educational Implications:

The considerations for ethical engagement of youth living with HIV in the research process identified in this study may be used to review and refine existing International and National guidelines that act as a guide for investigators, ethics committee members and research staff. These findings should supplement broader ethical education including principles of beneficence, non-maleficence, autonomy and justice.

Authors’ Biographical Sketches

Ashley Chory: Ashley Chory is a Research Program Manager at the Arnhold Institute for Global Health at the Icahn School of Medicine at Mount Sinai. Her research experience and interests focus on adolescent health. For this study, she resolved conflicts in article screening between EG and NC, and reviewed all drafts of the manuscript.

Winstone Nyandiko: Prof. Winstone Nyandiko is a professor at Moi University College of Health Sciences, and his primary research interests include pediatric and adolescent HIV in western Kenya. He contributed to the conception of the idea for this review and revised the manuscript.

Emma Gillette: Emma Gillette is a Clinical Research Coordinator at the Icahn School of Medicine at Mount Sinai, where her main research interests are global health, pediatric HIV, and the development of youth-friendly HIV services. She has experience coordinating research which engages children and adolescents living with HIV, and for this review she conducted the literature search, screened the articles, wrote the first draft of the manuscript, and incorporated co-authors’ insights.

Michael Scanlon: Michael Scanlon is the Assistant Director of Research at Indiana University, and his primary research interests include pediatric and adolescent HIV, particularly through the use of qualitative methods. His contributions to this review included idea conceptualization and reviewing of manuscript drafts.

Josephine Aluoch: Josephine Aluoch is a Research Program Manager at AMPATH. Her primary research interests include pediatric and adolescent HIV. In this study, she reviewed manuscript drafts and provided overall insight.

Dennis Munyoro: Dennis Munyoro is a Peer Navigator for AMPATH. His research interests focus on pediatric and adolescent HIV in western Kenya, and he has experience facilitating research involving CALWH. For this study, he reviewed drafts of the manuscript.

Celestine Ashimosi: Celestine Ashimosi is a Research Coordinator for AMPATH. Her research interests focus on pediatric and adolescent HIV in western Kenya, and she has experience facilitating research involving CALWH. For this study, she reviewed drafts of the manuscript.

Whitney Beigon: Whitney Beigon is a Peer Navigator for AMPATH. Her research interests focus on pediatric and adolescent HIV in western Kenya, and she has experience facilitating research involving CALWH. For this study, she reviewed drafts of the manuscript.

Janet Lidweye: Janet Lidweye is a Research Assistant for AMPATH. Her research interests focus on pediatric and adolescent HIV in western Kenya, and she has experience facilitating research involving CALWH. For this study, she reviewed drafts of the manuscript.

Jack Nyagaya: Jack Nyagaya is a Research Assistant for AMPATH. His research interests focus on pediatric and adolescent HIV in western Kenya, and he has experience facilitating research involving CALWH. For this study, he reviewed drafts of the manuscript.

Allison DeLong: Allison DeLong is a biostatistician and data scientist in the Center for Statistical Sciences at the School of Public Health at Brown University in Providence, RI, USA. She has contributed to numerous studies of CALWH based in Kenya and other settings. For this study, Allison reviewed the criteria for the literature search and provided comments on the methods and presentation of results.

Rami Kantor: Rami Kantor is a Professor with the Division of Infectious Diseases at the Brown University Alpert Medical School. His research interests include infectious diseases, including adult and pediatric HIV. On this project, he provided detailed oversight from idea conceptualization to careful review of manuscript drafts.

Rachel Vreeman: Dr. Rachel Vreeman is the Chair and Director of the Department of Health System Design and Global Health, and her research interests primarily include pediatric HIV, health system development, and adolescent health. She provided expertise for the conceptualization of the idea for this review, and careful review of all manuscript drafts.

Violet Naanyu: Prof. Violet Naanyu is a Professor at the Moi University School of Arts and Social Sciences. Herr research interests focus on pediatric HIV, particularly through the use of qualitative methods. For this project, she provided review of final manuscript drafts.