Adolescents’ and young women’s perspectives on participation in biomedical clinical trials for HIV prevention in Tanzania and India: A qualitative inquiry

Abstract

Adolescent girls and young women are disproportionately affected by HIV in many lower-resource settings. These individuals are often excluded from early clinical trials for new HIV prevention products, thus delaying potential access. We explored adolescent girls’ and young women’s (AGYW) perceptions of HIV risk, perspectives on trial participation, and understanding of research concepts. Individual or repeated in-depth interviews were conducted with a total of 43 AGYW. Interviews were conducted in participants’ language of choice, audio-recorded, transcribed, and translated into English. Thematic analysis was applied. A total of 21 participants were enrolled from Dar es Salaam, Tanzania, and 22 from Pune, India. HIV risk perception varied by country, with Tanzanian participants often describing risk as behaviors tied to economic factors, and Indian participants describing risk as behaviors associated with limited HIV knowledge, inequitable gender norms, and pervasive sexual violence. Trial participation was largely viewed as acceptable; however, concerns were raised regarding standard recommendations for using condoms and contraception during trial participation, and the potential for side effects. Research concepts were notably challenging for participants to understand, particularly the concept of placebo. Although adult involvement was perceived as useful support in Tanzania, it was deemed essential for trial participation in India. Participants in our study described a need for and potential benefits of new HIV prevention products. Taking into consideration the local context, clinical trials with adolescent girls and young women should ensure understanding of research requirements and concepts, minimize preventive misconceptions, and consider involvement of a trusted adult.

Introduction

Globally, adolescent girls and young women (AGYW) are disproportionately affected by HIV (UNAIDS, 2019, 2022). Tanzania and India provide distinct, yet important examples of this. In Tanzania, HIV prevalence among AGYW aged 15–24 is 2%, while the prevalence among adolescent and young men is 1.4% (Brown et al., 2018). In India, specific data on AGYW are hard to come by as the National AIDS Control Organization does not often disaggregate their survey data on individuals aged 15–49 (Mehra et al., 2016). Nevertheless, current data reveal the prevalence of HIV among women aged 15–49 is 0.19% and 0.22% among men of the same age group (National AIDS Control Organization & ICMR- National Institute of Medical Statistics, 2022).

In many countries, HIV infection among AGYW is partially attributed to widespread gender inequality; this inequality can manifest as a greater likelihood of having sex partners who are older, an early age of marriage, an inability to negotiate condom use, and in some cases, sexual violence (UNAIDS, 2019). Despite this, many AGYW are likely to perceive themselves as at low risk of HIV acquisition (Afriyie & Essilfie, 2019; Price et al., 2018; Schaefer et al., 2019).

Recent advancements have led to the development of new biomedical HIV prevention options such as oral and injectable pre-exposure prophylaxis (PrEP) – options that have the potential to subvert gender norms and related HIV infection among AGYW, as they are user initiated and do not require partner contribution. Yet, the clinical trials necessary to advance these options have largely focused on adult women aged 18 older (Bekker et al., 2020; Bekker et al., 2018; Machado et al., 2017; Skoler-Karpoff et al., 2008). Excluding adolescents in clinical trials results in missed opportunities to evaluate product safety, effectiveness, and tolerability of novel products in a timely manner (Abdool Karim et al., 2012). Furthermore, it limits the ability to assess barriers and facilitators to product use (Amico et al., 2017; Velloza et al., 2020), and it reduces timely access of new products by many of those most vulnerable to HIV (Jaspan et al., 2008).

Increasingly, researchers are addressing these concerns (Machado et al., 2017; Pack et al., 2019; Simons-Rudolph et al., 2020), including by implementing a clinical trial designed to assess outcomes related to PrEP use among adolescent girls under the age of 18 in South Africa, Uganda, and Zimbabwe (HIV Prevention Trials Network). Yet, progress has been slow, with only a limited number of Phase I, II, or III trials being conducted among non-pregnant AGYW globally (NCT04778514 (ages 16–24), NCT05458765 (ages 15–24), NCT04994509 (ages 16–25 ) (Gill, Happel, et al., 2020; Gill, Johnson, et al., 2020; Stranix-Chibanda et al., 2021; Yager et al., 2022).

Ethical, legal, and regulatory challenges have all been found to limit adolescent participation in clinical trials. These include parental consent, insufficient understanding of research concepts, mistrust of research, and a lack of perceived benefits from trial participation (DiClemente et al., 2010; Kapogiannis et al., 2018; Knopf et al., 2020; Nakalega et al., 2021). There have also been practical concerns that have limited adolescent participation, including concerns that adolescents would miss more study visits, be more lost to follow-up, or be less adherent to use of study products than their older counterparts (Schenk et al., 2014).

Given increasing efforts to include young people in clinical trial research, it is worth examining the benefits and challenges of adolescent participation in trials in lower-resource settings. More specifically, in this paper, our study aims are to explore: 1) HIV risk perception, 2) concerns related to potential inclusion in HIV prevention trials, and 3) understanding of research concepts among adolescent and young women (age 15–21) in Tanzania and India. These two countries were chosen not only because they represent distinct and important examples of how HIV disproportionately impacts AGYW, but also because of existing relationships between researchers in these locations.

Materials and methods

This study is a secondary analysis of qualitative data collected as part of a larger mixed-methods NIMH funded study (R01MH086160) entitled “Adolescent Women & Microbicide Trials: Assessing the Challenges & Opportunities to Their Participation” (ClinicalTrials.gov #NCT00872261). Details of the original study are published elsewhere (Tolley et al., 2014). Briefly, the impetus was to investigate challenges and opportunities related to including AGYW in future HIV prevention trials in Tanzania and India. One component of this multi-phase study was in-depth interviews with AGYW.

Eligible participants for this study included AGYW aged 15–21 living in Dar es Salaam, Tanzania or Pune, India, who reported having had a sexual relationship within the last three months. Study team collaboration with representatives from community-based organizations, schools, and government leaders facilitated the identification and recruitment of participants from a variety of settings, such as clinics, youth centers, schools, NGOs, and public areas known as adolescent hang-outs (Baumgartner et al., 2015; Pack et al., 2019; Tolley et al., 2014). Purposive sampling ensured participants represented a range of potential risk contexts: single and married; in- and out-of-school; currently or previously engaged in sex work. Per local ethical guidelines, all participants aged 16–21 provided written informed consent prior to participation in the study, and for those aged 15, parental written informed consent was obtained, and 15-year-olds provided written informed assent. We note that the age of majority in both Tanzania and India was 18 years old and therefore we considered adult young women as ages 18–21 and adolescents as ages 15–17. This age break of under 18 versus 18 or older also aligns with common global clinical trial eligibility criteria.

Four female research assistants (RAs) in Tanzania and four female RAs in India, all trained in qualitative interviewing techniques, utilized semi-structured interview guides. Questions solicited information about participants’: living situations; relationships; perceived HIV risk; interests and concerns about trial participation for HIV prevention products; and understanding of research concepts. As published previously, definitions of research concepts were provided verbatim to all participants to ensure a basic understanding, while follow-up questions assessed the depth of understanding (Pack et al., 2019). Per the protocol, participants were offered opportunities to complete the interview in up to three separate meetings; this flexibility enabled the discussions to be conducted in parts, at a pace and a schedule convenient to participants. For each meeting, interviews, lasting approximately one hour, were conducted in private locations identified by the participants. Interviews were audio recorded, transcribed, and when necessary, translated into English (from Hindi or Swahili).

Transcripts from Tanzanian and Indian participants were analyzed via Excel to facilitate team-based analysis. Analysts applied thematic analysis following a process of reading, coding, developing analytic memos, and creating matrices for data reduction purposes (Tolley E.E., 2016). First, transcripts were read for familiarity. An initial codebook was developed a priori with structural codes based on the interview guide; emergent codes were subsequently identified through iterative reading and memo writing. Excel matrices were created by two PhD level qualitative researchers and a Masters in Global Health student to identify major themes within and across participants and to identify illustrative quotes. Previous analyses suggest our sample size was more than sufficient for reaching saturation (Hennink & Kaiser, 2022). Our qualitative research adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) Checklist (see Appendix).

Primary ethical approvals for this study were obtained from Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania, the National Institute for Medical Research in Tanzania, the Maharashtra Association of Anthropological Sciences (MAAS) Institutional Ethics Committee in India, and FHI 360’s Protection of Human Subjects Committee. Approvals for analysis of secondary data were also received from UNC-Chapel Hill, Duke University and Northwestern University as these institutions are affiliated with current authors.

Results

A total of 43 AGYW were included in this analysis. Participants from Tanzania (n=21) included 10 adolescent girls (aged 15–17) and 11 young women (aged 18–21), while Indian participants (n=22) included 3 adolescent girls and 19 young women. Participants from both countries were diverse in relationship status, years of education, and engagement in sex work (Table 1). Results from our thematic analysis revealed five major themes described below. In brief, they include the following: 1) HIV risk perception varies by country; 2) concerns about trial participation were largely tied to the need to use condoms and contraception, and the potential for unwanted side effects; 3) benefits of trial participation were recognized by participants; 4) research concepts were challenging for AGYW to understand; and 5) adult involvement may be necessary for some to consent to trial participation.

Table 1:

Demographic characteristics of participants

	Tanzania			India
	Adolescent Girls (15–17) N=10	Young women (18–21) N=11	Total N=21	Adolescent Girls (15–17) N=3	Young women (18–21) N=19	Total N=22
Age (mean)	16.4	19.6		15.7	19.7
Relationship status
Single	6	7	13	0	7	7
Married	4	4	8	3	12	15
Years of education (mean)	7.2	9.3		4.3	9.9
Currently in school	2	3	5	0	1	1
Currently out of school	8	8	16	3	18	21
Engaged in sex work	1	2	3	0	7	7

HIV risk perception varies by country.

Perceived HIV risk is a likely precursor to interest in participating in an HIV prevention trial and thus an understanding of this context by country was explored. In Tanzanian participants, norms around behaviors that could lead to increased HIV risk were largely viewed as pervasive and tied to economic factors, while perceptions of personal risk and the ability to limit risk varied by age. All participants indicated AGYW in their communities are at risk of HIV due to participation in unsafe sex and the normalization of having multiple sex partners. For example, some explained:

Because they have engaged in sex issues, that’s why they are at risk, and many of them do not use condoms. (Tanzanian, Single, Age 16, Attending school)

If you have one boyfriend and you stick with just one boyfriend, nowadays you seem like a rural person – rustic. They tell you that you need to have a bucket and container (two men helping you, ndoo na kidumu). (Tanzanian, Single, Age 20, Attending university)

Half of these participants mentioned economic factors, such as poverty and the desire for additional spending money, as the driving force behind engagement in risk behavior.

Perceptions of personal HIV risk in Tanzania differed between age groups. Many more young women than adolescent participants voiced concerns about their higher risk of HIV infection because they could not trust their partners.

I am so worried because personally I do protect myself, but I don’t know about my husband. You can protect yourself, but your husband might infect you with HIV. That is the way so many people are infected with HIV in that way because you can be settled, but your partner does not put that in his mind. (Tanzanian, Married, Age 20)

In contrast to their older counterparts, nearly all adolescent participants expressed uncertainty about their own risk, though some explicitly viewed their risk as low due to negative results of HIV testing, and trust in the fidelity of their partners.

Perceived control to reduce HIV risk also differed between age groups. Almost half of the young women believed they have limited control as they were not using protection and were unsure of their partners’ sexual behavior. A young woman explained: ‘my only control is just asking him to use condoms.’ (Tanzanian, Married, Age 20). Half of the adolescents, however, perceived themselves as having high/sufficient control over reducing HIV risk even though they reported similar levels of risk behaviors (e.g., number of partners, condom use, HIV testing) as young women did.

In India, while sexual behavior among AGYW was acknowledged, it was considered necessarily covert, particularly sex before marriage. Personal risk perception and the perceived ability to prevent HIV risk were tied to limited knowledge, pervasive violence, and inequitable power dynamics within participant’s sexual relationships. Among Indian participants who were asked about HIV risk perception of AGYW in general, several acknowledged that girls engage in risk behavior. This was largely defined by participants as having sex before marriage or having multiple sex partners, though a couple of participants described this behavior as ‘characterless’ and necessarily covert. For example:

Interviewer: Our society says that girls are not sexually active before marriage.

Participant: What do they know? In India girls do “do it”. But in India, girls do not have the courage to come out in the open and say so. Many of them do it. (Indian, Single, Age 21, Out of school)

Lack of knowledge about HIV was mentioned as a driving factor for increased risk. This was mirrored in the personal experiences shared by Indian participants, as two young women noted they had never heard of condoms before, and several explained they had only seen them on television or heard about them in passing; they did not have personal experience or know how to correctly use them. Furthermore, nearly all married participants claimed they did not know about sex before they were married.

My aunt told me… she said “if your husband touches you then do not shout. Keep quiet.” (Indian, Married, Age 15)

I was scared. I didn’t know anything… I wasn’t allowing him to come near me. There was no one. (Indian, Married, Age 21)

Sexual violence was also mentioned as a driving factor for HIV risk. Two separate sex workers expressed concern about young women in their profession, noting ‘many atrocities are happening with the girls here’ (Indian, Married, Sex Worker, Age 21), including instances where women are ‘beaten’ (Indian, Married, Sex Worker, Age 20), ‘scorched’ with cigarette butts (Indian, Married, Sex Worker, Age 21) and gang raped (Indian, Married, Sex Worker, Age 21). Yet the experience of sexual violence was not limited to sex workers. Half of all Indian participants mentioned experiencing physical or sexual abuse themselves, with one noting the frequency of forced sex within marriage:

[W]e read about rape incidents. We say such and such girl was raped by so and so. Rape means to have sexual relations with a girl or woman without her willingness. This happens with many girls and women by their husbands. Why do we not call them rape? (Indian, Married, Age 21)

Personal HIV risk perception for many, regardless of risk context, was directly tied to the behavior of one’s partner(s). As one participant explained:

I don’t feel the threat now but… Who knows about a man’s attitudes? If a wife goes to her parents’ house, the man is likely to keep relations with other women. (Indian, Married, Age 17)

Perceived control to reduce HIV risk was generally low among Indian participants. Lack of autonomy and inequitable power dynamics were mentioned by many. Those who were married described an inability to purchase items for themselves and the need to obtain permission and/or have a chaperone to leave the home. One young woman explained:

I am not supposed to sit near the door. I must remain in the house all the time. I am not supposed to go to someone’s house. These are the things I don’t like about my husband... When I am all the time in the house I feel as if I am caged. (Indian, Married, Age 19)

Among sex workers, most also described having limited financial control, as they needed to provide madams, husbands, and partners with a portion of their earnings.

Concerns about trial participation were largely tied to the need to use condoms and contraception, and the potential for unwanted side effects.

In both Tanzania and India, participants did not generally express concerns about trial-related activities including potential participation for 6 to 12 months, using study products, receiving HIV testing, and undergoing gynecological exams, particularly if exams were conducted by female doctors. Nevertheless, concerns about the standard ethical practice of recommending condom use for individuals participating in clinical trials for new HIV prevention products were mentioned by many. In both countries, participants indicated their partners would likely refuse to use condoms. In Tanzania, a couple of participants also mentioned that their own lack of pleasure while using condoms would likely inhibit use, while in India, several participants noted their unfamiliarity with condoms would be challenging if condom use were required.

Oh! That! I feel that is somewhat difficult... How to wear it? We do not understand. We have not seen anyone using it… If we do not remember or understand, then we will find it difficult. (Indian, Married, Age 15)

For several participants in both countries, using a contraceptive method, often a clinical trial inclusion criterion, was also mentioned as a concern. These participants anticipated it would be difficult for married women as sustained contraceptive use would require agreement among family members.

They have to face familial pressures. If it has been only a year of her marriage, she will have to postpone the pregnancy as she wants to be a part of the study. The mother-in-law will say, “She got married after you and became pregnant, how come you did not?” (Indian, Married, Age 21)

In both countries several participants, from varying risk contexts, explained they were concerned that study product use could lead to unwanted side effects.

My concerns are that if those things [study product] will hurt me later, will I be attended [cared for] there? (Tanzanian, Single, Age 17, Not attending school)

We will fear that if we take this every day, we might face some side effects. (Indian, Married, Age 21)

The majority of participants in Tanzania indicated they thought it would be easy to use the study product as indicated in a clinical trial, while in India, some concern over daily use was expressed by several participants of varying risk contexts. For example, one sex worker noted,

But if I don’t have any customers on some day then what is the necessity? Then why should I consume that pill? (Indian, Married, Age 20, Sex Worker)

Among Indian participants in general, the need to ask permission from one’s partner, husband, or mother-in-law to attend study visits, and the potential for stigma associated with risk behavior were mentioned as concerns by a few participants, though these views were not shared explicitly by those in Tanzania.

Benefits of trial participation were recognized by participants.

In Tanzania, all participants expressed perceived benefits of trial participation. They viewed HIV testing and medical exams as informative for their own health and easier to access through the trial than on their own. One adolescent participant explained:

You go and get tested; you know your health status first because, as for me until now, I have not been tested. That means when I go for testing and start participating in that study, I will know my health and if I have other diseases, I get to know. Isn’t that one of the benefits? That means you start treating yourself even before you start suffering so much. (Tanzanian, Married, Age 16, Not attending school)

Furthermore, participants viewed trial participation as an opportunity to acquire information about HIV and HIV prevention:

I want to know more about what destroys us girls so much with this disease. I want to know what is making us more the victims of this disease. (Tanzanian, Single, Age 17, Not attending school)

In India, personal benefits to participating in clinical trials were not discussed in detail. However, in both countries, the potential discovery of a new HIV prevention product for AGYW was seen as a substantial benefit.

In today’s world, the issue of HIV prevention is based on men because I don’t think women use female condoms. Most of the time it is men who agree to wear condoms. Then you can hope that you are protected from HIV. So, by using [microbicide] gel or [PrEP] pills you will be on the safe side that you are protected from getting it. (Tanzanian, Single, Age 21, College student)

I feel there must be preventive measures to stop HIV infection, and teenagers must have knowledge about them. (Indian, Married, Age 21)

Research concepts were challenging for AGYW to understand.

Participants in both countries struggled to understand the research concepts such as use of placebo, randomization, and blinding, regardless of their age or education level. Transcripts revealed that interviewers explained research concepts several times; even then, some participants still expressed difficulty demonstrating understanding of concepts in their own words. In India, several participants seemingly did not want to discuss research concepts, opting to skip questions altogether which the team interpreted as indicating that the questions were too difficult.

Among the research concepts, ‘placebo’ appeared to be the most difficult concept for participants who struggled to understand why a placebo was needed in clinical trials. Several participants noted they would expect protection from HIV as a trial participant, explaining that any study drug should contain essential ingredients. For example, a couple of participants noted:

What I think, she should get the drug that contains the ingredient. (Tanzanian, Single, Age 16, Out of school)

If you give the medicine, then one should obviously feel good. (Indian, Married, Age 20)

Most participants viewed randomization as fair because it helped to avoid favoritism and bias; this concept however was linked to the misconception that study products would be equally effective.

Adult involvement may be necessary for some to consent to trial participation.

In both countries, the majority of participants mentioned the importance of involving key adults in the informed consent process, despite acknowledgement that such involvement may make it difficult for adolescents to participate in trials. The rationale, however, differed by country.

In Tanzania, participants noted adult involvement would be useful for educating and advising adolescents, for instance, on how to use the study product and research concepts. And a young woman explained:

If a problem happens or an adolescent gets a disease during the trials, parents or guardians would know about it. (Tanzanian, Married, Age 20)

In India, most participants suggested AGYW would only be able to participate in a trial if they have received permission. Husbands and mothers-in-law were perceived to be the primary sources for permission. This was illustrated by a participant who explained:

You were mentioning my own wish, but I am still telling you that it is not possible. My husband as well as family members should give me permission. (Indian, Married, Age 17)

Discussion

This secondary analysis of in-depth interview data explored adolescent and young women’s perspectives (AGYW) on participation in biomedical clinical trials for HIV prevention products in Dar es Salaam, Tanzania and Pune, India.

In-depth interviews with AGYW revealed HIV risk perception differed by country. Participants in both countries noted AGYW are at risk of HIV, yet risk behavior, including having multiple sex partners, was expressed in more normative terms from participants in Tanzania compared to those in India where sex outside of marriage, and having multiple sex partners, was more highly stigmatized. Furthermore, although young women in Tanzania indicated they were personally at risk of HIV, adolescents reported uncertainty about their risk. This is a key finding, as previous analyses, have revealed that exposure to risk factors such as sex without condom use and partner abuse are likely similar between the two groups (Tolley et al., 2014). In both countries, participants tied their personal risk perception to the perceived behavior of their partner(s). This is consistent with other studies noting women tend to assess HIV risk largely on the basis of their partner’s personal qualities and behavior, perceptions of infidelity in the relationship, and their subjective feelings of being respectfully treated (Scorgie et al., 2021). However, the lack of HIV knowledge, and pervasive experience of sexual violence was even more notable among Indian participants of varying ages and risk contexts.

In contrast to previous general concerns that adolescents may be more non-adherent to trial protocols than adults (DiClemente et al., 2010), qualitatively, our study participants from Tanzania felt confident that they could participate in trials for 6–12 months, visit the clinic monthly, get tested for HIV, undergo other medical procedures (i.e., gynecological exams), and use the study products as indicated. This finding supports previous studies reporting inclusion of adolescents aged 16–17 years did not impact negatively on trial implementation and maintain the scientific integrity of the study (Abdool Karim et al., 2012; Schenk et al., 2014). Nevertheless, it is important to note the lack of autonomy expressed by Indian participants who described a need to seek permission from husbands and mothers-in-law to leave the home and use contraceptives, including condoms. For additional country context, condoms have been widely available in both Tanzania and India for a long time, and HIV testing services, per policy (but not necessarily practice), have been available for those younger than 18 in Tanzania if they meet certain criteria such as ‘sexually active’; and services could be in available in India if adolescents were in another high-risk group (e.g. sex work) but it appears most community-based testing still focuses on ages 18+ (34, 35, 36).

Our findings from Tanzania revealed all adolescent participants argued they should be involved in clinical trials for HIV preventive products for various reasons including access to perceived benefits such as HIV testing and information about their general health status. This is consistent with a Kenyan study which found that 15–19-year-olds were willing to participate in an HIV trial so as to receive HIV-related education, HIV testing, and pre/post-test counseling (Simons-Rudolph et al., 2020). Given adolescents’ largely positive perspective on trial participation, it is critical to ensure that the trial environment is comfortable for adolescents, such as maintaining continuity in research staff and providing youth-friendly study personnel (DiClemente et al., 2010). Although participants from India did not discuss their own interest in trial participation as much as those in Tanzania, they did express a need for HIV education and new prevention products. As such, researchers can modify trial designs to integrate education sessions with health check-ups, in areas where these benefits may be key motivations for participation.

Understanding research strategies and concepts was complex and difficult for participants of all ages in both Tanzania and India. ‘Preventive misconception’, or the overestimation of protection offered by an intervention yet to be proven efficacious, was common. This may result in raising a false sense of security offered by trial participation, increasing the probability of HIV infection, and introducing concerns about informed consent (Ndebele et al., 2014; Sugarman et al., 2019). Given that adolescent girls are a particularly vulnerable subject population, preventive misconception needs to be carefully considered when involving them in clinical trials for HIV prevention as it has been identified in previous studies among adolescents (de Bruyn et al., 2008; Giocos et al., 2008; Ott et al., 2013).

In our study, most participants indicated it would be important to involve key adults in the consent process. Like ours, some studies examining barriers and facilitators to future participation of adolescent and young people in HIV vaccine trials have revealed the importance of ensuring the target population is both fully informed and supported by community members who can help with recruitment and retention efforts (Mbunda et al., 2014; Mbunda et al., 2016). Yet, other studies argue not requiring parental consent could be a seemingly effective approach to recruit adolescents from certain sites for several reasons. Adolescent girls can feel free from inadvertent disclosure and admission of sexual activity to their parents; they may also potentially avoid negative repercussions that might be more likely in families with domestic violence (Baumgartner et al., 2015). And, in the United States, a recent study found that parental involvement in the consent process did not influence adolescents’ willingness to participate in HIV prevention trials (Knopf et al., 2023). These mixed findings suggest is important for researchers to know the local contexts.

Regardless of the context, however, researchers should be reasonably prudent in the informed consent process considering each adolescent’s intellectual maturation and cognitive capability. The consent process can be enhanced by providing extended discussion with trained peer nurse counselors, scheduling a separate enrollment visit to allow sufficient time for learning about the trial, implementing an evaluation to assess understanding, and completing consent in the participants’ language of choice (Abdool Karim et al., 2012; Kass et al., 2015; Knopf et al., 2020; Simons-Rudolph et al., 2020). This knowledge transfer may be challenging; however, our findings offer additional evidence to support decision making regarding adolescent consent (Gilbert et al., 2015).

Furthermore, we argue it is important to ensure adolescents’ autonomy to decide whether to inform their parents or not and which adult would be involved in the process of informed consent. Many AGYW study participants from Tanzania experienced familial violence (Baumgartner et al., 2015), and this may be barrier to trial participation for those who fear violence from disapproving parents or family members. Ensuring expanded autonomy and letting adolescent girls choose whether adults should be involved may lower such barriers and provide more opportunities to girls considering trial participation.

This study has several limitations. First, as with all qualitative studies, our results cannot be considered generalizable, although we do think our sample population was representative of adolescent young women who could potentially benefit from biomedical products. In addition, this was a secondary analysis of data collected during a period when HIV prevention clinical trials were focused on both pills and vaginal gels. However, since that time, there has been very little research into how AGYW feel regarding clinical trial participation for HIV prevention products. Without their input and without considering how best to include them in clinical trials, we are doing a disservice to AGYW. This paper should serve as a reminder that more work is needed to ensure new HIV prevention options are made available to all who need them. That said, we also note another study limitation which was that in India, we were unable to get IRB approval to interview single adolescents ages 15–17 (we had permission for married only) even though our own work reveals that key stakeholders in India disagreed with the ethical rulings (18).

Though this study focuses on answers about general perspectives on prevention products in clinical trials, our analyses may have been biased if participants were thinking beyond more pill-focused clinical trials. As adolescent girls and young women in our study were recruited from Dar es Salaam and Pune, their perspectives may be primarily limited to experiences living in urban settings. Adolescent girls living in rural areas may have different concerns, such as transportation for access to the trial site or confidentiality. There is also potential response bias of adolescent girls to provide socially acceptable responses to questions about sexual behavior. Nevertheless, we trained the interviewers to be sensitive and comfortable while asking such questions and maintained the same interviewer when multiple interviews were conducted.

Recruitment and retention of AGYA was for this qualitative formative phase was challenging, particularly in India. However, from our perspective, this further supports the need to include diverse AGYW in clinical trials for new HIV prevention products. The majority of participants who did not complete the full interview were highly vulnerable to HIV due to pervasive sexual violence and accompanying limited autonomy. The stories they shared were painful and, although perhaps incomplete, they deserve recognition. Ensuring AGYW with increased vulnerability to HIV are included in future clinical trials is critical, though will likely be difficult, as indicated by our own challenges with study recruitment and retention.

It is not only ethical, but also imperative to include AGFYW in clinical trials for new HIV preventative products to ensure they have knowledge and timely access to the prevention they need (Rosenthal et al., 2018). As global research collaborations continue conducting biomedical clinical trials for HIV prevention trials, our study reveals the need to consider local contexts for adolescent inclusion.

Biographical Note.

APP is a Research Assistant Professor within the Feinberg School of Medicine at Northwestern University in the United States. HJ is an Assistant Manager within the National Health Insurance Service in the Republic of Korea. SK is a Professor and Dean in the School of Medicine at Muhimbili University in Tanzania. JS is a Senior Research Fellow in the School of Medicine, Nursing, and Health Sciences at Monash University in Australia; previously she was a Doctor of Community Medicine in India. AM is a Research Coordinator in the School of Medicine at Muhimbili University in Tanzania. JH is a Project Coordinator in the TEACCH Autism Program at the University of North Carolina at Chapel Hill in the United States. EET is a Senior Behavioral Scientist and a Research Director at FHI 360 in Durham, North Carolina in the United States. JNB is an Associate Professor in the School of Social Work at the University of North Carolina at Chapel Hill in the United States.

Data Availability

Data cannot be shared publicly because: 1) adolescents are considered a vulnerable population and the information collected by this study is sensitive; 2) the data cannot be fully de-identified; and 3) our IRB approval letters from Tanzania and India do not allow sharing the raw data publicly. Nevertheless, the dataset used during this current study may be available upon reasonable request from the first author’s (APP) institution Northwestern University (IRB # STU00215531; irb@northwestern.edu) and in consultation with the study PI (EET).