Acceptability and preference research play a crucial role in the design, evaluation, and implementation of any new product in any geographical setting. They also play a critical role in the development of clinical guidelines and policies [22]. A wide range of acceptability studies have been conducted in diverse general and key populations for HIV prevention products including women, adolescent boys and girls, men who have sex with men (MSM), female sex workers (FSWs), people who inject drugs (PWID), and transgender women (TGW) [23-26]. These studies have focused on prevention products such as oral and injectable PrEP, vaginal and rectal microbicides, vaginal rings, and future HIV vaccines [22,26-29]. The main drivers of prevention product adoption and uptake include product effectiveness, cost, absence of side effects, and multipurpose protection against sexually transmitted diseases and pregnancy [30]. Acceptability studies have shown that emotional and intuitive decision-making for a product choice is also driven by factors such as sexual satisfaction, dimensions of trust, self-efficacy, and sociocultural environments [26,31]. There is evidence for differential preference for prevention products among different populations. For example, in South Africa, FSWs preferred injectable products over oral PrEP and microbicide gel, adolescents preferred a potential HIV vaccine and expressed dislike for a vaginal ring, and MSM preferred rectal microbicides [24,25]. Relative importance of specific product attributes also varied across target populations. For example, the route of PrEP administration was found to be the most important attribute for prospective end-users in Peru, Ukraine, India, and Botswana; FSWs in Kenya; and young women in South Africa [32], whereas the PrEP dispensing site was the most important attribute for participants from Uganda and MSM in South Africa and the second most important attribute for FSWs in Ukraine [32].

There are several standard qualitative methods for assessing the acceptability of an intervention for the target population and setting. Two common methods are focus group discussions (FGDs) and in-depth interviews (IDIs). Moderated FGDs allow for understanding of group dynamics including similarities and differences and allow to probe further on particular topics as they come up in the discussion. This type of interaction generally results in a deeper understanding of the forces in a community that may impede or facilitate the implementation of effective interventions. IDIs are conducted in a one-on-one setting with members of the target communities. They allow for deeper probing to understand more details, have nuanced understanding of sensitive topics, and have an opportunity to monitor changes in tone and body language, which is also an important factor in eliciting key responses.

For the successful development and adoption of any product, it is critical that perspectives from all service providers including health care professionals and community “gatekeepers” are taken into account in the development process [33,34]. Thus, there is a need to gather evidence from diverse populations and multitude of related stakeholders across geographies in India and focus on understanding their perspectives on potential new products such as bNAbs and preferences of different product attributes. These are often conducted through key informant interviews (KIIs).

In India, acceptability and feasibility studies have been conducted for various microbicides and PrEP [35-42]. These studies have been scattered over time and have been restricted to a few geographical locations and key populations. Thus, there is a need to gather evidence from diverse populations and multitude of related stakeholders across geographies in India and also focus on perspectives with respect to the potential new product—bNAbs.

Apart from the aforementioned methods, there are other qualitative research methods that are necessary to complement some of the emerging insights from the potential end-users. It has often been observed that studies conducted to explore preferences for hypothetical products or willingness to participate in hypothetical trials have shown differences in the stated preferences and intentions versus the eventual decisions and observed behavior of end-users [43-45]. In Kenya, an observational cohort study reported a 90% willingness to participate in future trials; however, during actual trial recruitment, only 30% were willing to actually enroll [44]. In a real-time scenario, end-users may be presented with multiple contextual trade-offs as well as nonconscious factors that may influence their decision-making, and hence, stated versus revealed preferences may be different [45]. It has also been reported that hypothetical choice experiments with end-users provide relatively satisfactory predictive results for positive choices, but they are less effective for predicting negative choices [43]. Thus, to premeditate and elicit the “say-do” gap, one of the useful methods deployed by behavioral scientists is to identify and analyze shortcuts known as heuristics in action, which take off the cognitive load of decision-making and help anticipate and explain potential avenues for gaps between the stated intention and action [46,47].

The cognitive process marking the final behaviors exhibited and decisions made by prospective end-users may be a mix of conscious and nonconscious factors and, hence, cannot always be brought out through in-person discussions alone. Therefore, the application of behavioral science in a simulated context has been found to be extremely beneficial for deciphering the key drivers of decisions and behaviors. In such a situation, the participants in a study do not just have to talk about their past or future decisions but have to actively make a decision in real time in a simulated environment. This provides researchers with a better understanding of the decision pathways of prospective end-users as well as potential aspects of say-do gaps to inform the design and development of products. Toward this, Ethnolab is a behavioral research methodology that often uses a Conundrum game [48] to deploy scenarios based on the preliminary qualitative research findings in a simulated environment and observe user choices in real time. The method has been used in several sociobehavioral and acceptability studies for health programs and interventions, including voluntary male medical circumcision decision-making in Zimbabwe and Zambia [48]; understanding HIV prevention for adolescent girls and young women (AGYW) in South Africa [49]; and estimating the impact of nonconscious drivers of human behavior among pregnant women and mothers of infants as well as with frontline workers on reproductive, maternal, newborn, and child health outcomes in Uttar Pradesh [50].

Acceptability may be defined as the extent to which people delivering or receiving a health care intervention consider it to be appropriate based on anticipated or experienced cognitive and emotional responses to the intervention [55]. Several theoretical frameworks are available for understanding acceptability of new HIV prevention products or technologies [41,42,55-57] at the individual and community levels. A recent systematic review proposed a model of acceptability of health interventions, the Theoretical Framework of Acceptability (TFA) [55]. According to TFA, intention to use a health intervention is determined by seven factors: (1) perceived effectiveness, (2) intervention coherence, (3) affective attitudes, (4) burden, (5) ethicality, (6) self-efficacy, and (7) opportunity costs. It was chosen to adapt the TFA to guide exploration of acceptability of bNAbs in this study as it can readily incorporate individual- and community-level influences on attitudes and behavior. The study design was also informed by the conceptual framework developed by Mensch et al [56] to incorporate the various factors operating at individual, interpersonal, community, and structural levels in influencing a person’s product-related attitudes and perceptions. In addition to adopting aspects from the social-ecological model, the framework emphasizes the role of actual product-related factors, including product attributes, which also play a role in defining an individual’s preferences [56]. Thus, guided by these frameworks, an adapted conceptual framework was used to design this study. In this adaptation, the constructs were embedded within three domains (Figure 1) [55,56]:

There are multiple factors at the health systems and programmatic levels that service providers such as frontline health care providers, policy makers, and program managers at national, state, and district levels would consider as key issues that are needed for introduction and uptake of bNAbs as HIV prevention products in the future. Thus, complementing the study’s conceptual framework for acceptability, which will be used among the end-users, there is a need to have a conceptual framework to assess the feasibility. For this purpose, the framework shown in Figure 2 [58] was adapted from the WHO Framework on Health Systems, which was also used by the WHO for reviewing the impact of new vaccine introduction on immunization and health systems. The broad themes include the following:

The following sample selection criteria will be followed for the abovementioned methods.

A total of 30 FGDs (2 FGDs per end-user group per site; for 5 end-user groups across 3 sites) and 45 IDIs (3 IDIs per end-user group per site; for 5 end-user groups across 3 sites) will be conducted in Delhi, Mumbai, and Chennai to investigate factors at individual, interpersonal, and sociostructural levels that facilitate or impede the acceptability of bNAbs among susceptible communities in India.

The SBE will mirror the sampling frame and the broad respondent profiles from the FGDs and IDIs. Keeping in mind that Ethnolab elicits the most useful insights in small and intimate settings, the sample would include 6 participants for each end-user group (distinct and different from the participants in the FGD or IDIs) across each site. Thus, the total sample size would be 90. Each instance of Ethnolab will have 6 respondents, and a total of 20 Ethnolab-based SBEs will be conducted across all 3 sites.

In addition, 5 KIIs will be conducted with health care service providers and policy makers in each region, amounting to a total of 15 KIIs. Thus, the total sample size of the qualitative component of the study is expected to be approximately 300 (FGD: 30×8=240, IDI=45, and KII=15).

The implementing partners for the study are YR Gaitonde Centre for AIDS Research and Education (YRGCARE), Centre for Sexuality and Health Research and Policy (C-SHaRP), and The Humsafar Trust (HST), who will be responsible for conducting the FGDs, IDIs, and KIIs. The designing of the Ethnolab game–based data collection method will be done by Final Mile and IAVI. Final Mile, in working with other study partners (YRGCARE, C-SHaRP, and HST), will be responsible for the implementation and conduct of the SBE sessions across all study sites.

Data from FGDs, IDIs, and KIIs will be collected using semistructured interview topic guides. Trained research staff will conduct the FGDs, IDIs, and KIIs. The research staff will receive additional training specific to the content of this study and research ethics. SBEs will be conducted by partner consultants and will also include a round of initial meetings with the other study clinical research center partners to ensure alignment with the findings from the FGDs and IDIs.

For the FGDs and IDIs among end-users, the following broad areas will be covered in the lines of inquiry:

The topic guide will be translated into native languages (Hindi, Tamil, Telugu, or Marathi), back-translated into English, and then revised in the original language. All discussions will be audio-recorded, transcribed, and translated. They will be deidentified before proceeding for further data analysis. Each FGD and each IDI will span over 60 to 90 minutes.

The SBE sessions will consist of three parts:

The data generated from the games, along with the ensuing conversations, will help elicit behavioral insights and identify intrinsic drivers and extrinsic factors influencing the preferences and decisions of prospective end-users. The Ethnolab play will last for approximately 60 minutes, and the subsequent group discussions will last for 45 minutes. The overall activity will not exceed 2 hours. The session will involve engaging games to maintain a playful environment, and adequate breaks will also be incorporated to ensure that the time of engagement does not become burdensome for the participants.

Semistructured interview guides will consist of 10 to 12 open-ended questions and scripted probes. The interview guides will be translated into native languages (Hindi, Tamil, or Marathi), back-translated into English, and then revised in the original language. Key informants for each study population will be asked questions for the need perception of a prevention product, preference and importance of product attributes, social and cultural acceptability, risk compensation, health systems readiness, and alignment with the policy environment in India. Each KII will be conducted for approximately 90 minutes.

The qualitative approach will use triangulation to strengthen and ensure the accuracy of data [65]. According to Denzin and Lincoln [66], triangulation is a process in which several methods are used in the study and might be used in four basic ways: (1) data triangulation, (2) methods triangulation, (3) theory triangulation, and (4) researcher triangulation. In this study, data triangulation, methods triangulation, and researcher triangulation will be used. All transcripts will be redacted (to remove any personally identifying information that might inadvertently have been recorded) and uploaded into NVivo (Lumivero) or Dedoose (University of California). First, a line-by-line review of the transcripts will be performed, and first-level codes will be identified to create a common a priori codebook (based on the adapted conceptual or theoretical framework and topic guides). All codes will be then entered and tagged to associated chunks of text. Texts corresponding to each of the first-level codes will be coded by at least 2 independent analysts and reviewed by senior investigators. Explanatory or theoretical or etic (researcher generated) codes will be arrived at using a constant comparative method [67].

The SBE results will be analyzed using the cognitive and emotional appraisal framework [68] as a base. Appraisal theories are componential theories that view an emotional episode as involving changes in a number of organismic subsystems and components. The components could include an appraisal, a motivational, a somatic, and a motor component. The framework will be used to generate the codebook and will then feed into the 4 major categories of context, emotions, mental models, and decision levers. This will be done along with the ranking of preferences drawn from the experiential game data. The SBEs will be analyzed to gain an in-depth understanding of (1) preference construction and (2) preference reversal.

Data source triangulation and researcher triangulation will enhance the reliability and trustworthiness of the findings [69]. Thus, study implementation and data analysis will also incorporate researcher reflexivity and researcher triangulation by maintaining “quicknotes” (a brief summary of every interview or focus group by the interviewers or moderators that will be shared with the analysts and investigators for feedback), writing memos, and engaging in peer debriefing to maintain ongoing awareness of our social location and how it may influence the research process and interpretation. A maximum of 2 interviewers or moderators will be used for every population of interest to ensure that there is minimum bias in the way questions are asked or follow-up probes are used.

Names or other personal identifiers will not be collected from the participants. Only the investigators and key research staff at the participating research sites will have access to the transcripts or translated text and digital recordings. As soon as an interview is completed, the audio file will be transferred from the digital recorder to password-protected computers. Subsequently, the file will be deleted from the digital recorder. The transcriptionist and translator will sign a confidentiality pledge stating that they will not reveal any information from the interviews to anyone else. The digital copies of transcripts and translated text will also be stored on password-protected computers.

Only this study’s research staff at the participating research site will have access to the audio files, transcripts, and translated text. All digital recordings will be redacted, and any personal identifying information will be removed. Digital recordings will be deleted after 1 year (the 1-year delay is to ensure that there are no gaps in the transcripts). Redacted transcripts will be maintained for 2 years and then destroyed. Informed consent forms will be separately stored and will include signs, initials, or “X” marks rather than names. Unique identification codes will be assigned to all individual records, including digital recordings and transcripts. Hard copies of the data and related documents will be stored in a secure location in locked cabinets in the offices of study and will be accessed only by the research staff.

The study was presented to the institutional review boards (IRBs) of all 3 implementing partners (HST, C-SHaRP, and YRGCARE), and all comments received were adequately addressed in the protocol. The approved protocol (HST-IRB-50-01/2021; C-SHaRP/0007327/220; YRGCARE-359) will be implemented for data collection and analysis.

Participants for IDIs, KIIs, FGDs, and SBEs will be presented with an information sheet that outlines the scope of the study and a consent form that provides options to sign or put initials or put an “X” mark. This approach has been accepted by the IRB for other previous studies. Given the potentially low literacy levels of some participants, the research assistants will offer to read and explain the information sheet and consent form to the participants. As part of the informed consent process, all potential participants will be informed that their decision to participate or not in interviews or games will not affect the services they currently receive or may receive in the future from their respective community agencies.

Participants in the FGDs, IDIs, and SBEs will receive an honorarium of INR 500 (US $6.25) for participating in the study. This amount is based on input from the community advisory boards of the study partners in India. This covers the costs incurred for roundtrip transportation. If the focus group or IDI participants elect to withdraw from the study during data collection, they will still receive compensation. Key informants will receive INR 1500 (US $18.75) (wherever applicable), and this is proposed from previous learning wherein key informants reported loss of wages owing to their participation and suggested that an honorarium should be instituted for KIIs to minimize such experiences. All interviews will be conducted in person, and honorariums will be in cash.

There are no direct benefits to participants for taking part in this study. However, the participants will be better informed about the various HIV prevention options currently available across the globe and the options under development. The study has the potential to benefit the society and the participant’s communities if the data collected are found effective and are adopted in routine service delivery or for further informing bNAb research.