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Creating a Theoretically Grounded Gaming App to Increase Adherence to Pre-Exposure Prophylaxis: Lessons From the Development of the Viral Combat Mobile Phone Game

Creating a Theoretically Grounded Gaming App to Increase Adherence to Pre-Exposure Prophylaxis:... Background: In the United States, young minority men who have sex with men (MSM) are most likely to become infected with HIV. The use of antiretroviral medications to reduce the risk of acquiring HIV infection (pre-exposure prophylaxis, PrEP) is an efficacious and promising prevention strategy. There have been significant advances regarding PrEP, including the definitive demonstration that PrEP reduces HIV acquisition and the development of clinical prescribing guidelines. Despite these promising events, the practical implementation of PrEP can be challenging. Data show that PrEP’s safety and effectiveness could be greatly compromised by suboptimal adherence to treatment, and there is concern about the potential for an increase in HIV risk behavior among PrEP users. Due to these challenges, the prescribing of PrEP should be accompanied by behavioral interventions to promote adherence. Objective: This study aimed to develop an immersive, action-oriented iPhone gaming intervention to improve motivation for adherence to PrEP. Methods: Game development was guided by social learning theory, taking into consideration the perspectives of young adult MSM who are taking PrEP. A total of 20 young men who have sex with men (YMSM; aged 18-35 years) were recruited from a sexually transmitted infection (STI), HIV testing, and PrEP care clinic in Jackson, Mississippi, between October 2016 and June 2017. They participated in qualitative interviews guided by the information-motivation-behavioral skills (IMB) model of behavior change. The mean age of participants was 26 years, and all the participants identified as male. Acceptability of the game was assessed with the Client Service Questionnaire and session evaluation form. Results: A number of themes emerged that informed game development. YMSM taking PrEP desired informational game content that included new and comprehensive details about the effectiveness of PrEP, details about PrEP as it relates to doctors’ visits, and general information about STIs other than HIV. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with health care providers; decreasing stigma; and a focus on personal relevance of PrEP-related medical care. Behavioral skills themes centered around self-efficacy and strategies for adherence to PrEP and self-care. Conclusions: We utilized youth feedback, IMB, and agile software development to create a multilevel, immersive, action-oriented iPhone gaming intervention to improve motivation for adherence to PrEP. There is a dearth of gaming interventions for persons http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 1 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al on PrEP. This study is a significant step in working toward the development and testing of an iPhone gaming intervention to decrease HIV risk and promote adherence to PrEP for YMSM. (JMIR Serious Games 2019;7(1):e11861) doi: 10.2196/11861 KEYWORDS cell phone; HIV; young adult; sexual and gender minorities reported video gaming occurs on portable devices [18,21,22]. Introduction The widespread appeal and use of mobile phones and video game playing creates a unique opportunity to deliver health Background education to diverse YMSM on PrEP during leisure time, outside The primary prevention of HIV infection remains a crucial of the clinic, and in a manner that is cost-effective and easily priority. In 2016, there were 39,782 new HIV diagnoses in the scalable [24-27]. United States, and 67% of these new diagnoses were of gay and Interactive game play has been shown to enhance players’ bisexual men [1]. HIV also disproportionately affects motivation to improve health behaviors and self-care in a variety communities of color. Despite only comprising 12.6% of the of clinical settings and populations. Games can attract and US population, nearly 45% of all new HIV infections occur maintain attention, a key component for effective behavior among African Americans. The use of antiretroviral medications change. Compelling interactive phone-based games can expose to reduce the risk of acquiring HIV infection (pre-exposure players to essential health-related content thousands of times prophylaxis, PrEP) is an efficacious and promising new and also give players unlimited opportunities to rehearse new prevention strategy [1,2]. There have been significant advances skills and receive personalized feedback on health choices made regarding PrEP including the definitive demonstration that PrEP within the game [28-30]. Games have been shown to be reduces HIV acquisition. Despite promising data, the practical efficacious in promoting fitness, improving weight management, implementation of PrEP is challenging [3-10]. Unfortunately, and improving safer sex skills [27,28,30,31]. For example, an individuals who are often at the highest risk of HIV infection HIV and AIDS prevention computer game called Life Challenge and eligible for PrEP come from populations that historically was developed by the New York State Department of Health have been underserved by health care [11,12]. Therefore, to enhance safer sex negotiation by adolescents and young engaging diverse persons on PrEP in care is challenging, and adults. The game showed significant improvement in reinforcement and support for patients and doctors is required self-efficacy for partner negotiation and condom skills for those [11,13-15]. Behavioral Interventions promoting adherence to who started with the least self-efficacy [30]. Two pregnancy comprehensive PrEP treatment and healthy sexual behaviors prevention games, The Baby Game and Romance, designed for will need to be tailored to diverse, underserved, and at-risk sexually active young adults, showed trends in improving populations and will need to reinforce the clinician-patient knowledge and attitudes about parenting and unprotected sexual relationship. behaviors [29]. Video games have also been applied to improve In addition, the behavioral interventions accompanying PrEP self-management skills and healthy behaviors in those living need to be scalable, cost-effective, and easily integrated into with asthma, diabetes, and cancer [32-36]. For example, a video clinical settings [2,16]. Without these necessary components, game named Re-Mission (tested with adolescents and young integration of behavioral interventions into clinical settings adults aged 13-29 years) was designed as an action-adventure cannot be realistically sustained. Utilizing gaming technology in which the main character shoots cancer-causing agents in the to deliver behavioral interventions for young men who have bloodstream. In a randomized control study, 375 male and sex with men (YMSM) can improve intrinsic motivation and female participants who played Re-Mission had significantly information and build behavioral skills for adherence. The use improved adherence to trimethoprim-sulfamethoxazole of an intervention that utilizes gaming technology is particularly (TMP/SMX; P=.01) and 6-mercaptopurine (P=.002) after an compelling for use with younger adults, as this age group is at average of only 10.7 hours of play. Adherence to TMP/SMX the highest risk of acquiring HIV and this age group has most by those playing Re-Mission was 19% greater than those in the actively inquired about PrEP in clinical settings. In addition, control group. Self-efficacy (P=.01) and knowledge (P=.03) 72% of young male adults in the United States say they play also increased [35,36]. Thus, appealing interactive games can video games often or sometimes [17]. Gaming technology is target information, motivation, and skills for medical care and also popular among minority men who have sex with men have led to a broad spectrum of desirable health outcomes (MSM), the subgroup most at risk for acquiring HIV. In the including increases in knowledge, attitude changes, and past, gaming was mistakenly identified as a primarily adolescent increased medication adherence [27,31,37-39]. and heterosexually dominated activity, but current data support Gaps in Literature that gaming is actually quite diverse [18]. MSM gamers, referred to as gaymers in pop culture and mainstream articles, are highly Despite the promise and popularity of digital games, there is a represented on the web and increasingly shape the market paucity of interventions or publications related to gaming for [19-21]. In addition, within the United States, African Americans persons on PrEP [40]. Relatedly, there are games in development aged 18 to 35 years represent the most active and fastest growing for YMSM either living with HIV or at risk for HIV [41-45]. user group of mobile phones [22,23], and more than half of the For example, our research group has developed a gaming http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 2 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al intervention to improve antiretroviral treatment (ART) aims for continuous design testing and adaptation based on adherence for youth and young adults living with HIV that continuous feedback [53]. informs the development of this game [40]. LeGrand et al have Sample and Recruitment published a description of the development phase of a game Males aged between 18 and 35 years were eligible for entitled Epic Allies. Epic Allies is designed to improve ART enrollment in the study according to the following criteria: (1) uptake, engagement in care, and adherence among HIV positive English-speaking, (2) currently taking PrEP, (3) reported having YMSM and transgender women who have sex with men. While sex with other men, and (4) able to give consent and not playing Epic Allies, users can earn medals and tokens for taking impaired by cognitive or medical limitations as per clinical medications and reading health-related studies. [42]. Another assessment. Those who did not meet the abovementioned intervention called PlayForward aims to reduce the risk for HIV inclusion criteria were excluded. We recruited 20 YMSM for among at-risk, ethnic, and racial minority adolescents. This qualitative interviews to guide game development after tablet-based game provides an interactive world using an avatar institutional review board’s (IRB) approval. Subjects were from where players face challenges such as peer pressure to drink a convenience sample recruited from a PrEP clinic in Jackson, alcohol or engage in other risky sexual behaviors [43]. A mobile Mississippi, between October 2016 and June 2017. Subjects phone–optimized intervention entitled healthMpowerment is were approached by research staff with an IRB-approved flyer, designed to reduce sexual risk behaviors among YMSM. In this and written consent was obtained upon meeting with study staff intervention, YMSM can acquire reputation points through for the qualitative interview. Overall, 20 subjects were reading information about HIV, playing sexually transmitted approached over the course of the interviews, and all of them infection (STI)–related games, and through positive interactions consented and completed the interview. Subjects were recruited with other users. Despite the promise and popularity of digital until data saturation was achieved, and a relative balance in the games, there are no published or presented abstracts related to sample was achieved based on age greater than 26 years versus gaming for persons on PrEP that we could find. younger. The mean age of participants was 26 years (range: This Study 18-35 years; 11 out of the 20 were younger than 26 years). A We developed a gaming intervention to improve adherence to majority of the participants (17/20, 85%) identified as African PrEP for YMSM aged 18 to 35 years. This intervention American, 100% (20/20) identified as MSM, 70% (13/20) integrates a smart pill bottle cap (that measures adherence) with completed 12th grade, 75% (15/20) had been taking PrEP longer an iPhone game. The gaming intervention was informed by the than 6 months, 75% (15/20) reported missing a dose of PrEP information-motivation-behavioral skills (IMB) theory of in the previous week, 45% (9/20) reported missing 3 doses or learning. The IMB model, consistent with social learning theory, more in the previous week, and 75% (5/20) had been taking is broadly applicable and can be used to guide game PrEP for 6 months or longer. development and create theoretically consistent gaming content Procedures [46-50]. The iPhone gaming app was designed for participants The study was approved by the hospital’s IRB, and participant to experience absorbing action-oriented adventures that increase consent and interviews were conducted in a private room located information about their health (eg, knowledge about PrEP and in a PrEP clinic in Jackson, Mississippi. Interviews were HIV prevention and adherence), improve motivation (eg, action conducted by 1 of the 2 MDs (psychiatrists) with support from figures experience health benefits of adherence to PrEP), and a trained research assistant, and subjects were reimbursed US build skills (action figures interact with clinicians at $50 per survey (for a total of US $150) for their time. The appointments, take medications as prescribed, and practice safe psychiatrists who conducted the interviews did not provide sex; see Multimedia Appendices 1-13). Adherence (measured medical or clinical services in the HIV clinic. Interviews lasted by the smart pill bottle cap) and game-related text messages are between 45 and 60 min and were digitally recorded. As we integrated into the gaming intervention. Multiple reviews have adapted our gaming intervention from games that were already demonstrated that behavioral interventions shown to be most developed (Dr. Nano X and BattleViro), the system and the efficacious are those tailored for the target population and framework (eg, code, database, and design) were already in preceded by formative research to inform intervention place at the beginning of the project. Adaptations to the game development [51,52]. The aim of this study was to describe the occurred as themes emerged from the interviews [41]. Biweekly development of this iPhone gaming app entitled ViralCombat. meetings were held with the programmers to discuss all adaptations, including changes to content, game graphics Methods framework, and game messaging. Gaming App Development Adaptation of the Information-Motivation-Behavioral Development of ViralCombat was accomplished using iterative Skills Adherence Gaming Intervention and collaborative procedures to integrate the clinical experiences The IMB gaming app for persons on PrEP, entitled ViralCombat, of YMSM taking PrEP, academic researchers, and technology was adapted from the popular Mission Critical Studios game partners. Game development was guided by qualitative entitled Dr. Nano X as well as our previously developed game interviews with a group of MSM aged between 18 and 35 years for persons on ART entitled BattleViro [40,41]. Dr. Nano X is taking PrEP. Guided by the principles of agile software a 5-star-rated mobile game (the highest rating possible) in the development [53], the qualitative interviews and the game and iTunes app store and is available on both Android and iPhone. app programming were synergistic. Agile software development http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 3 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al The ART adherence game, named BattleViro, has been storyboard of the game and completed interviews. When the previously described in the Journal of Medical Internet Research iPhone version became available, 9 participants were given the [41]. We worked directly with the development team at Mission game on an iPhone, and their feedback was elicited through an Critical Studios to develop ViralCombat using Dr. Nano X and interview. Therefore, qualitative feedback was received from BattleViro as a basic framework. Adapting our game to promote all 20 participants. The interview guide consisted of focused PrEP adherence from already existing games greatly decreased but open-ended questions aimed at maximizing participant the cost of the project. Characters, actions, and IMB messaging responses (see Textbox 1). Participants were asked about about PrEP were built specifically for ViralCombat; however, information relevant to medication adherence, motivating factors we were able to reuse backgrounds, mechanisms of game play to adherence, and behavioral skills needed for adherence. The and controls, and many sound effects from Dr. Nano X and IMB model guided interview content, and participants were BattleViro [54,55]. ViralCombat game levels are distinct from also queried about their general gaming experience and their those in BattleViro, and they include organ systems such as the reactions to the storyboard and gaming content. penis, anus, and mouth. Information Needed for Adherence We worked iteratively with youth living with HIV and Mission Participants were asked about knowledge and information that Critical Studios to create the app. The game starts with a influences their adherence to PrEP and engagement in medical 45-second narrative movie that explains the storyline and game appointments. Questions included: objectives. The player is told by the narrator, in a deep and What type of information from doctors or friends dramatic voice, “you have been chosen, due to your smart makes it easier to take PrEP? decisions and healthy choices, to be cloned and shrunken in order to enter your own body to destroy attacking viruses and What information makes it easier to come to PrEP infections.” The narrator emphasizes that “in order to acquire related appointments? ammunition and strength, you must take you medication in real This part of the interview aimed to understand the specific life and also pick up pills during play.” Players are given a knowledge about HIV and PrEP that promotes adherence tutorial on game actions and can also design their individual behaviors. For example, some probes focused on how side and diverse characters. As players successfully battle HIV, effects and other health-related information can influence engage with providers, and take medication, they move to new, adherence to medication and care (for more examples, see distinctive levels (arterial system, penis, anus, and mouth). Textbox 1). Messages from the doctors, nurses, and friends encourage and Motivation for Adherence provide clues during difficult twists and turns in the battle. Answering quiz questions from clinician avatars allows each Participants were queried about motivational issues related to player to earn strength and points; wrong answers are corrected adherence to PrEP with probes such as: and explained. Players find medication, strength, and points by I would like to hear about what you think the serious acting on positive suggestions. During each mission, the player’s issues are surrounding PrEP and taking medications score (pill count and health) is shown. All character control and to prevent HIV, gaming is done by touch screen technology on the phone; no What are the things that make it hard to take PrEP? additional accessories are needed for play. Throughout the game, the terms “HIV” and “PrEP” are seen on the screen, but they This part of the interview was dedicated to understanding both are never part of an audio feature, so stigmatizing information personal and social motivations for adherence to PrEP. Queries cannot be overheard by another person. The game-related text were focused on the positive and negative attitudes toward messages have gaming graphics, similar to other apps and taking PrEP, perceived negative effects of nonadherence to games, and the app uses push notifications to engage gamers PrEP, and the individual’s perceptions of social support from in play. If players were less than 90% adherent during the week, significant others, family, friends, and medical care providers phrases such as “Missing you in Combat” and “Get back in the (for more examples, see Textbox 1). game” are texted to their phones. Congratulatory short message Behavioral Skills for Adherence service (SMS) text messages such as “Great job in battle” and “You are fighting off virus well” are sent for greater than 90% Participants were also asked about their ability to perform adherence (see Multimedia Appendix 2). Throughout gaming, necessary adherence and HIV preventative tasks and their the mission stays the same: kill the virus and build strength perceived self-efficacy for these tasks. Questions included: through taking medicine, learning information, improving What are the ways that you stay safe from HIV? motivation, and engaging with healthy characters to improve What are the ways that you remember to take PrEP adherence to PrEP and build HIV preventative skills. and remember your PrEP related appointments? Interview Topics What events in your life make it harder to remember Interviews with YMSM taking PrEP-guided game development to take PrEP? Or remember your appointments? were conducted. A total of 11 participants were shown the http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 4 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Textbox 1. Qualitative interview guide based on the information-motivation-behavioral (IMB) skills model. Information What knowledge or information about HIV and pre-exposure prophylaxis (PrEP) is helpful to know? What knowledge or information helps you to take PrEP daily? Does knowing about side effects change decision making around taking PrEP? Motivation What are the main issues in coming for PrEP related medical appointments? What are the things that make it hard to take PrEP? What are the attitudes or feelings that people like you have that make it harder to take PrEP? Or easier to take PrEP? How do partners, your family, and your community play a role in adherence to PrEP related care? Behavioral skills Do you use alarms, your phone, or reminders to remember to take PrEP? What do you do if you miss a dose of PrEP? What are the strategies for adherence to PrEP over time and across different situations? Are there things that you do such as eating, or avoiding certain substances, that make taking PrEP easier? General gaming attitudes What is your reaction to getting some PrEP related and HIV related information and skills in a game? Do you ever play games that teach you facts or in which you learn something? Do you go online or use your phone to learn information about your health? Have you ever played a health-related game before on your phone or at a computer? Reactions to ViralCombat What did you like and not like about the game? What do you think this activity is trying to teach you? How much did the material look like the other games that you play? How could this activity or content be improved for others like you? Now that you have seen this game, would you want to play it? Before you came here today, did you ever find anything like this on a game on a phone or on a computer? Would you be worried about playing the game when others could see it? What would you say if someone asked you about the game? We also asked participants about strategies for General Gaming Attitudes self-reinforcement for adherence over time and across different Participants were also asked about their general attitudes and situations. We asked questions such as: experiences with games. Participants were asked questions such as: Do you consciously think about your PrEP medication schedule on a long-term basis? What games do you, or people you know, play on the What strategies have you used or developed to cellphone? remember to take PrEP or to go to your appointments What types of graphics, avatars, and rewards do you based on your activities? like? And what do you not like? This part of the interview aimed to assess perceived abilities How are games useful? Do you develop any skills and strategies to store, obtain, and self-cue the use of when you play games? medications despite challenges and across situations (for more These queries elicited descriptions of popular game activities examples, see Textbox 1). and attitudes about gaming. The responses were used to make the format and game mechanics of ViralCombat engaging and immersive (for more examples, see Textbox 1). http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 5 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al 3=“Mostly satisfied”; 2=“Indifferent or mildly dissatisfied”; ViralCombat Storyboard and iPhone Game and 1=“Quite dissatisfied”) [56]. We did not calculate an alpha Participants were asked for feedback about the storyboard or coefficient for this sample because of the small number of the iPhone game (once the mobile game was ready) with the participants completing the CSQ (n=9). In other studies, the probes such as: internal consistency of the CSQ-8 is high, with alpha coefficients What was the main point of this activity? ranging from .84 to .93 for the CSQ [58]. The SEF contains 13 items that assess the feasibility and perceived utility of activities What could you learn from this activity? in the game. For example, the SEF states: “I will be able to Would you recommend this type of game to your apply what I learned from this game in my life” (for which the friends? response options are 1=“Strongly agree”; 2=“Agree”; What is your reaction to having some HIV and PrEP 3=“Disagree”; and 4=“Strongly disagree”) [57]. As the SEF related information and skills in an iPhone game? asks about specific the utility of separate elements of the After the first version of the game was developed on the iPhone, intervention, and not about singular constructs, alpha coefficients participants were asked additional and modified probes such for the SEF are not commonly calculated. as: Data Analysis Is the game easy to navigate and easy to understand? Qualitative Data Did any part of the game not work? Trained research assistants transcribed verbatim the digital audio Are there other topics that the game should cover that recordings of each interview. Then, the MD- or PhD-level it does not? research team member reviewed the transcripts with the digital Answers to these questions guided the iterative development recording for accuracy. Qualitative data analysis followed the of the game levels, actions, characters, and graphics (for more tenets of thematic analysis, which consisted of sequential steps examples, see Textbox 1). [59,60], and interviews continued until data saturation was achieved. The research team familiarized themselves with the Medication Adherence Monitoring Tracking and data, reviewing each transcription. Next, the research team met Game-Related Text Messages weekly and generated a list of codes as they emerged. The team Participants were also asked about the electronic pill monitoring generated a thematic table of the analyses and checked the extent organizers and adherence-related text messages. We queried to which the emerging themes reflected the coded data [59,61]. participants about the smart pill bottle cap that can electronically The team grouped the themes under the general categories of monitor, measure, and securely relay adherence pill bottle the interview guide (ART information, ART motivation, ART openings to our research team. Participants were asked about behavioral skills, general game attitudes, and reactions to the use of reminder messages with a game-related graphic. ViralCombat). Themes were examined in their relation to Feedback was elicited about game-related messages if players perceived utility of the game and for factors that would improve missed a dose using texted phrases such as “Missing you in or detract from the game’s impact. Team discussion and Combat” and “Get in the game.” Feedback was also received interviews continued until discrepancies were resolved. about SMS text messages if doses are taken on time such as “Great job in battle” and “You are fighting off virus well!” (see Quantitative Data Multimedia Appendix 2). Participant responses on the CSQ and SEF were entered into an Excel file, and responses were verified with a second entry. Quantitative Feasibility and Acceptability Data Categorical response frequencies were calculated for each item The game was developed iteratively. A total of 11 participants of both scales. General acceptability of the intervention is were shown the storyboard of the game for approximately 30 illustrated using individual items from the scales. CSQ items min; qualitative feedback was elicited, and game development are reported using the proportion of participants endorsing on the iPhone occurred. After the development of the iPhone satisfaction with the intervention (response options “Very version of ViralCombat, 9 of the 20 participants played the satisfied” and “Mostly satisfied” were combined). SEF items game for 45 to 50 min with the interviewer in the room (see are reported using the proportion endorsing “agreement” with Multimedia Appendices 1-13). These 9 participants were shown feasibility and utility of the game (response options “Strongly each of the game levels on the phone by the interviewer and agree” and “Agree” were combined). played each level. After playing the game, these 9 participants completed qualitative interviews, and then, written or Results quantitative feedback was obtained. Quantitative feedback was collected from these 9 participants using versions of the Client Reactions to ViralCombat Storyboard and iPhone Service Questionnaire (CSQ) and the session evaluation form Game (SEF) [56,57]. Both these instruments were developed to Interviews from both the storyboard and iPhone game revealed measure client satisfaction and perspectives on intervention a number of themes that guided game development. Participants aspects. The CSQ consists of 8 items that assess general desired informational game content that included new and satisfaction with the game. An example query from the CSQ is comprehensive details about PrEP, details about PrEP as it “In an overall, general sense, how satisfied are you with the relates to doctors’ visits, and general health information. game?” (for which the response options are 4=“Very satisfied”; http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 6 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Motivational themes that emerged were the desire for I think there should be facts in the game about other enhancement of future orientation; reinforcement of positive health stuff, about smoking and drinking on PrEP. influences from peers, partners, and friends; collaboration with Many participants also wanted more guidance through the levels. health care providers; decreasing stigma; and increasing personal For example, a 29-year-old white male participant stated: relevance of HIV prevention. Behavioral skills themes centered I would like better hints on each level on how to beat around self-efficacy and strategies for PrEP adherence and the level. medical care (see Textbox 2 for qualitative interview themes and resulting game adaptations based on the IMB model). An 18-year-old black male said (see Textbox 2): Textbox 2 highlights the barriers and facilitators to adherence Clues or hints when it gets hard would make this expressed by our participants and the corresponding gaming better. app action or message that was adapted to enhance facilitators Monitoring Pill Bottle Opening and Game-Related or challenge barriers. Textbox 2 also includes general gaming Text Messages attitudes that influenced the development of ViralCombat and We asked participants about the SMS text messages with gaming specific reactions to the ViralCombat storyboard and iPhone graphics and the use of a smart pill cap that measured adherence. game. In addition to the themes in Textbox 2, participants who During the interviews, we demonstrated how openings of the played the game on the phone said that important gaming pill bottle were measured wirelessly, and we showed participants characteristics included directly destroying and fighting off HIV sample adherence-informed SMS text messages. When looking in game play, earning health points by taking pills that looked at the smart pill cap, an 18-year-old black male participant like PrEP, a prologue or introduction with a dramatic voice-over, stated: and images about HIV and STIs that were relevant. Participants wanted levels that become increasingly difficult (for a sense of It’s cool how it links with game. accomplishment). Participants did not want HIV or PrEP in the It’s awesome that there is a bottle that knows what title of the game because of concerns about privacy and stigma you are doing. but wanted to fight graphics labeled “HIV” and wanted to see The feedback about the cap was extremely positive; however, the word PrEP during gaming. A 29-year-old black male a 19-year-old black male participant stated: participant said: The pill cap is OK, I don’t love how big it is. People I like that the organ systems are the penis and the can see it in my bookbag more. anus, it’s funny, but also realistic. It helped me learn about how infection with HIV happens. A 26-year-old white male described: A 30-year-old white male participant said: It would be better if it was a bit smaller, but I like that it can record when I take pills, that helps me. It was awesome to shoot HIV virus before it enters the body, and I like that HIV looked like it would Although 2 participants had negative remarks about the size of under a microscope. the pill bottle, 18 out of 20 participants responded they liked the cap design and did not think the size of the cap was an An 18-year-old black male stated: impediment to use. During interviews, participants were also I liked taking pills that look exactly like PrEP; it’s shown SMS text messages that corresponded to adherence data like my real-life. from the smart pill cap. Participants liked the proposed SMS A 21-year-old white male stated (see Textbox 2): text messages, and an 18-year-old black male described: It was cool that I am playing a game about These texts cue me to take my meds. preventing, that it was like tailored to me and my A 30-year-old black male stated: friends. I like the game pictures. I think my other friends who think about HIV would ...the texts made me smile and also I felt like they were like playing this. just for me. The music and sound is really awesome. A 35-year-old black male participant described: The game was iteratively changed as comments were received that indicated a need for alteration. For example, facts about The texts got me in the mood to play the game again. HIV prevention and the benefits of adherence to PrEP were Of the participants, 3 described that they wanted more variation made more sophisticated when multiple participants gave in the game-related texts: feedback such that they knew most of the information given in Seeing the same graphics again and again is boring. the game and that they wanted more detailed information about [35-year-old black male and a 19-year-old black male] side effects. Many participants also asked for information about substance use. A representative comment was from a 19-year-old An 18-year-old black male stated: black male who said: I would like more variety in the game texts. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 7 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Textbox 2. Qualitative interview themes and resulting game adaptations based on the information-motivation-behavioral skills (IMB) model. Information New and comprehensive details about pre-exposure prophylaxis (PrEP) and how PrEP prevents HIV Game includes complex and realistic information about PrEP. Participants fight off HIV in each organ. HIV is graphically represented. Facts about HIV and PrEP are imparted at every level. HIV is pictured. PrEP as it relates to doctors’ visits Terms and verbiage often used at PrEP-related doctor visits are used and defined in the game frequently. The importance of regular HIV testing and testing for other STIs is explained. General health information Participants learn about sexually transmitted infections that PrEP does not protect them from getting (gonorrhea, syphilis, herpes, genital warts, and human papillomavirus). Participants in the game receive messages about how exercise and healthy eating also affect health. Participants also receive messages about avoiding illicit substances and how illicit substances can increase risk behavior. Motivation Enhancement of future orientation Messages about staying healthy for family, friends, and children scroll through game. As gaming participant takes more pills and builds more health, they are able to move through levels, receive more artillery, and have more success staying healthy. Personal relevance of HIV Participants are shrunken down to enter into their own body to fight HIV. During game play, participants see how PrEP works to prevent HIV infection. Collaborating with health care providers Throughout the game, participants partner with doctors to advance to the next level, build strength, and collect artillery. Reinforce influences from peers, partners, and friends Scrolling messages remind gamers that staying healthy for partners, friends, and family is meaningful for themselves and for the loved ones in their lives. Decrease stigma Participants are empowered to kill HIV before it enters the body and gain points with each healthy decision. Adherence to PrEP is valued as healthy and smart decision-making. Behavioral skills Self-efficacy for PrEP adherence and PrEP-related medical care Solving problems and collecting pills or swallowing pills in the game leads to more points, which leads to more strength, more health, and more artillery. This leads to more game play. Perseverance throughout levels leads to success in the game. Strategies for medication adherence and self-care Scrolling messages encourage the participant to use PrEP, schedule routine doctors’ appointments, and ask providers or doctors questions about topics relevant to HIV prevention. General gaming attitudes Desire for games with levels, sound effects, and colorful graphics. Ability to earn points in the game and choose avatars Levels or organ systems become increasingly difficult (for a sense of accomplishment). Background music, sound effects, and dramatic voice-overs are included. Colorful graphics are included and change often. Choice of avatars is available. Participants earn points in the game by swallowing pills. Reactions to ViralCombat Desire for game action that is realistic with relevant information about PrEP and HIV prevention. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 8 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Participants can directly destroy HIV in game play, and graphics look like PrEP and HIV. Participants improve health and gain points in the game by taking virtual PrEP pills. Participants liked progression through organ systems, with information about PrEP and HIV that is pertinent to that organ system. Textbox 2). Specifically, game play was made easier with Acceptability and Feasibility written messages and hints throughout each level on how to CSQ and SEF scores were available from participants who move forward. We also improved narrated instructions at the played the game on the iPhone for 45 to 50 min. The responses beginning of each level to assist players. General health facts were generally quite positive, 88% (8/9) of the participants were about smoking, side effects of PrEP, and how substances such satisfied with the activities in the game, 77% (7/9) learned a lot as drugs and alcohol can increase risky behavior were from this game, 88% (8/9) thought the game was well organized, incorporated into the game to increase perceived relevance. We 77% (7/9) felt game topics were interesting, 100% (9/9) felt also incorporated more detailed information about HIV and they would recommend the game to a friend, 77% (7/9) felt how PrEP works to improve learning and interest. We also game topics stimulated their interest in the material, 100% (9/9) included a condom quiz game and information about other STIs felt that game topics were relevant to their lives, and 66% (6/9) (see Multimedia Appendices 7, 8, and 11). To improve SMS felt they were able to do the activities in the game (see Table text messages, we included emojis and designed 5 different 1). The gaming intervention was improved based on the above game-related SMS text messages utilizing a larger variety of acceptability and feasibility feedback from the CSQ and SEF game graphics based on participant feedback. and also on the feedback from the qualitative interviews (see Table 1. iPhone game acceptability and feasibility scores (N=9). Questionnaire or form Participants endorsing statement, n (%) Client Service Questionnaire How would you rate the quality of the game? 8 (88) Did you get desired information from the game? 6 (66) To what extent does the game’s content meet your needs? 7 (77) If a friend were interested in a similar program, would you recommend our game to him or her? 9 (100) How satisfied are you with the amount of information you have received in the game? 7 (77) Has the information you received helped you to deal more effectively with issues important to you? 8 (88) In an overall, general sense, how satisfied are you with the game? 8 (88) Would you come back to the game again? 9 (100) Session evaluation form I learned a lot from the game. 7 (77) I will be able to apply what I learned from the game in my life. 6 (66) I was able to do the activities in the game. 8 (88) The game was well organized. 7 (77) The topic of the game was interesting. 7 (77) The presentation of the information stimulated my interest in the material. 9 (100) The topics of the game were relevant to my life. 8 (88) The game was enjoyable. 8 (88) I would recommend the game to others. 9 (100) I felt comfortable during game play. 9 (100) Proportion of participants that endorsed “Very satisfied” and “Mostly satisfied.” Proportion of participants that endorsed “Strongly agree” and “Agree.” http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 9 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al this study repeatedly expressed having access to, and familiarity Discussion with, iPhones. This widespread use of iPhones facilitates the uptake of gaming apps in clinical populations. Therefore, mobile Principal Findings technologies such as mobile phone games and apps have a great In this project, we utilized in-depth interviewing, focused by potential to enhance medical care and prevention interventions social learning theory (IMB), to create an iPhone gaming for populations who are disproportionately affected by HIV and intervention to measure and improve treatment PrEP adherence other STIs. and decrease HIV risk for YMSM [46-48,53,62]. A number of Limitations themes emerged through qualitative interviews with young men that informed game development. We found that YMSM desired Findings should be interpreted in light of study limitations. First, informational game content that included comprehensive details our participants were recruited from a PrEP clinic in Jackson, about how HIV is transmitted, PrEP-related doctors’ visits, side Mississippi. This clinic may not be representative of all PrEP effects of PrEP, and general health information. Motivational clinics in the United States or internationally. Therefore, the themes or findings that emerged were the desire for enhancement generalizability of the data collected to inform the development of future orientation; the need for reinforcement of positive of the app is unknown and may be limited. Second, this study influences from peers, partners, and friends; and the promotion focused on individual PrEP user perspectives. It may be equally of collaboration with health care providers. Motivational themes important to integrate the perspectives of clinicians, friends, or also included decreasing stigma and increasing personal partners into the game. In the future, including friends and social relevance of HIV prevention. Behavioral skills themes or networks into gaming prevention programs could be novel and findings centered around self-efficacy and strategies for PrEP effective. Perspectives of partners, friends, and clinicians could medication and appointment adherence including regular HIV also lead to a more robust understanding of barriers and and STI testing. facilitators to adherence to PrEP and PrEP-related medical care. Therefore, future research could examine the utility of Using the IMB theory in the development of this game ensured integrating feedback from clinicians and friends into the gaming that the intervention was informed by decades of prevention app. Finally, this app was developed for the iPhone. research. This study demonstrates that qualitative assessment, Development of the app for Android devices could allow for social learning theory, and agile software development can greater availability of the game and could be a forthcoming step complement each other and are important components to the in the future phases of research. development of a tailored and clinically relevant app. Participant data were used throughout the development of the game and Conclusions informed the informational, motivational, and behavioral This study is a significant step in the development and testing skill-building components of the game. Using a storyboard of an iPhone gaming app to promote adherence to PrEP and provided the research team with opportunities to share concept PrEP-related medical care. The long-term goal of this research models with participants early on in the design process and program is to test ViralCombat in a randomized trial and gather feedback with respect to necessary modifications. Sharing examine if the game is effective in changing PrEP-related the iPhone game with participants as it was developed also attitudes and adherence-related behaviors. If the results appear allowed for necessary, incremental improvements. YMSM at promising, the research team can distribute the technology risk of HIV infection provided key qualitative insights with procedures for the intervention to relevant and interested clinics, respect to the content and design and process of the game. community-based organizations, the Centers for AIDS Research, Tailored games that are informed by those who will use them and AIDS Trials Networks. The app could also be made have more potential for effective integration and uptake in available on iTunes and Google Play (Android) for a nominal clinical settings [41]. fee. Although iPhone games are pervasive in popular culture, no There are many advantages to using newer interactive other gaming apps have been developed for YMSM on PrEP. technology to improve adherence rather than traditional Findings of this study highlight several important barriers and face-to-face counseling, including scalability, efficiency, and facilitators to PREP adherence for YMSM. Mobile interventions cost-effectiveness. As electronic games are highly appealing to have the potential to reinforce skills learned in the clinic and young men [25], they are a natural opportunity to deliver health require fewer resources to deliver patient-centered, education during leisure time and outside of the clinic evidence-based interventions [63]. Furthermore, apps and mobile [25-27,52]. Games can attract and maintain attention, which is phone games have the potential to engage YMSM in a key component for effective behavior change. Compelling interventions, who otherwise may not be willing or able to interactive games can expose players to essential health-related participate in intervention programs. content thousands of times and also give players unlimited Gaming and mobile apps also have the potential to advance the opportunities to rehearse new skills and receive personalized delivery of information and promote healthy decision-making feedback on health choices made within the game [28,35]. We in disproportionately affected populations, including minority are not aware of other adherence interventions that integrate men who often have less access to medical care and support medication adherence monitoring technology, SMS text [60]. National data from the Pew Research Center indicate that messaging, and a theoretically informed game to improve younger, ethnic and racial minority populations use mobile information, motivation, and behavioral skills for PrEP phones frequently [64]. The adolescents and young adults in adherence. An intervention with these components may http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 10 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al empower and engage YMSM, aid clinics, and result in improvements in health. Acknowledgments This publication was made possible with help from the Providence-Boston Center for AIDS Research (P30 AI 042853). The project described was supported by grant number R34MH104068 (MPI: LW, LKB) from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health. Conflicts of Interest LM is a member of the Gilead Sciences Advisory Board and receives compensation for consulting from Gilead Sciences, Inc. No competing financial interests exist for the remaining authors. Multimedia Appendix 1 ViralCombat main menu graphic. [PDF File (Adobe PDF File), 66KB-Multimedia Appendix 1] Multimedia Appendix 2 Example of a short message service text message to the participants. [PDF File (Adobe PDF File), 62KB-Multimedia Appendix 2] Multimedia Appendix 3 ViralCombat game menu. [PDF File (Adobe PDF File), 37KB-Multimedia Appendix 3] Multimedia Appendix 4 Short narrative movie at the beginning of the game. [PDF File (Adobe PDF File), 57KB-Multimedia Appendix 4] Multimedia Appendix 5 Players can design and individualize their game character. [PDF File (Adobe PDF File), 47KB-Multimedia Appendix 5] Multimedia Appendix 6 Players are shrunken down to be able to enter the body to fight off HIV. [PDF File (Adobe PDF File), 29KB-Multimedia Appendix 6] Multimedia Appendix 7 Answering questions with allied doctors and building knowledge help each player successfully move to the next level or area of the body. Example of questions answered incorrectly. [PDF File (Adobe PDF File), 46KB-Multimedia Appendix 7] Multimedia Appendix 8 Answering questions with allied doctors and building knowledge help each player successfully move to the next level or area of the body. Example of questions answered correctly. [PDF File (Adobe PDF File), 42KB-Multimedia Appendix 8] Multimedia Appendix 9 Example of a player gaining strength in the anus level by collecting health pills and condoms. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 11 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al [PDF File (Adobe PDF File), 23KB-Multimedia Appendix 9] Multimedia Appendix 10 As players travel through the bloodstream, they must fight off viruses and gain health pills. [PDF File (Adobe PDF File), 51KB-Multimedia Appendix 10] Multimedia Appendix 11 Throughout ViralCombat, players engage in various games in order to move on to the next level. In the Condom Sequence game, players must go through the correct sequence of steps for correctly using a condom. 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Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol 2006 Jan;3(2):77-101. [doi: 10.1191/1478088706qp063oa] 60. Arya M, Kumar D, Patel S, Street RL, Giordano TP, Viswanath K. Mitigating HIV health disparities: the promise of mobile health for a patient-initiated solution. Am J Public Health 2014 Dec;104(12):2251-2255. [doi: 10.2105/AJPH.2014.302120] [Medline: 25322292] 61. Guest G, MacQueen C, Namey EE. Applied Thematic Analysis. Thousand Oaks, CA: Sage Publications, Inc; 2012. 62. Starace F, Massa A, Amico KR, Fisher JD. Adherence to antiretroviral therapy: an empirical test of the information-motivation-behavioral skills model. Health Psychol 2006 Mar;25(2):153-162. [doi: 10.1037/0278-6133.25.2.153] [Medline: 16569106] 63. Gerbert B, Berg-Smith S, Mancuso M, Caspers N, McPhee S, Null D, et al. Using innovative video doctor technology in primary care to deliver brief smoking and alcohol intervention. Health Promot Pract 2003 Jul;4(3):249-261. 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US Smartphone Use in 2015 URL: http://www.pewinternet.org/2015/04/01/us-smartphone-use-in-2015/ [accessed 2019-01-21] [WebCite Cache ID 75aq2AOok] Abbreviations ART: antiretroviral treatment CSQ: Client Service Questionnaire IMB: information-motivation-behavioral skills IRB: institutional review board MSM: men who have sex with men PrEP: pre-exposure prophylaxis SEF: session evaluation form SMS: short message service STI: sexually transmitted infection TMP/SMX: trimethoprim-sulfamethoxazole YMSM: young men who have sex with men Edited by G Eysenbach; submitted 23.08.18; peer-reviewed by J Vandenberg, L Hightow-Weidman; comments to author 12.10.18; revised version received 05.12.18; accepted 09.12.18; published 27.03.19 Please cite as: Whiteley L, Mena L, Craker LK, Healy MG, Brown LK Creating a Theoretically Grounded Gaming App to Increase Adherence to Pre-Exposure Prophylaxis: Lessons From the Development of the Viral Combat Mobile Phone Game JMIR Serious Games 2019;7(1):e11861 URL: http://games.jmir.org/2019/1/e11861/ doi: 10.2196/11861 PMID: 30916652 ©Laura Whiteley, Leandro Mena, Lacey K Craker, Meredith Garver Healy, Larry K Brown. Originally published in JMIR Serious Games (http://games.jmir.org), 27.03.2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on http://games.jmir.org, as well as this copyright and license information must be included. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 15 (page number not for citation purposes) XSL FO RenderX http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JMIR Serious Games JMIR Publications

Creating a Theoretically Grounded Gaming App to Increase Adherence to Pre-Exposure Prophylaxis: Lessons From the Development of the Viral Combat Mobile Phone Game

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Abstract

Background: In the United States, young minority men who have sex with men (MSM) are most likely to become infected with HIV. The use of antiretroviral medications to reduce the risk of acquiring HIV infection (pre-exposure prophylaxis, PrEP) is an efficacious and promising prevention strategy. There have been significant advances regarding PrEP, including the definitive demonstration that PrEP reduces HIV acquisition and the development of clinical prescribing guidelines. Despite these promising events, the practical implementation of PrEP can be challenging. Data show that PrEP’s safety and effectiveness could be greatly compromised by suboptimal adherence to treatment, and there is concern about the potential for an increase in HIV risk behavior among PrEP users. Due to these challenges, the prescribing of PrEP should be accompanied by behavioral interventions to promote adherence. Objective: This study aimed to develop an immersive, action-oriented iPhone gaming intervention to improve motivation for adherence to PrEP. Methods: Game development was guided by social learning theory, taking into consideration the perspectives of young adult MSM who are taking PrEP. A total of 20 young men who have sex with men (YMSM; aged 18-35 years) were recruited from a sexually transmitted infection (STI), HIV testing, and PrEP care clinic in Jackson, Mississippi, between October 2016 and June 2017. They participated in qualitative interviews guided by the information-motivation-behavioral skills (IMB) model of behavior change. The mean age of participants was 26 years, and all the participants identified as male. Acceptability of the game was assessed with the Client Service Questionnaire and session evaluation form. Results: A number of themes emerged that informed game development. YMSM taking PrEP desired informational game content that included new and comprehensive details about the effectiveness of PrEP, details about PrEP as it relates to doctors’ visits, and general information about STIs other than HIV. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with health care providers; decreasing stigma; and a focus on personal relevance of PrEP-related medical care. Behavioral skills themes centered around self-efficacy and strategies for adherence to PrEP and self-care. Conclusions: We utilized youth feedback, IMB, and agile software development to create a multilevel, immersive, action-oriented iPhone gaming intervention to improve motivation for adherence to PrEP. There is a dearth of gaming interventions for persons http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 1 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al on PrEP. This study is a significant step in working toward the development and testing of an iPhone gaming intervention to decrease HIV risk and promote adherence to PrEP for YMSM. (JMIR Serious Games 2019;7(1):e11861) doi: 10.2196/11861 KEYWORDS cell phone; HIV; young adult; sexual and gender minorities reported video gaming occurs on portable devices [18,21,22]. Introduction The widespread appeal and use of mobile phones and video game playing creates a unique opportunity to deliver health Background education to diverse YMSM on PrEP during leisure time, outside The primary prevention of HIV infection remains a crucial of the clinic, and in a manner that is cost-effective and easily priority. In 2016, there were 39,782 new HIV diagnoses in the scalable [24-27]. United States, and 67% of these new diagnoses were of gay and Interactive game play has been shown to enhance players’ bisexual men [1]. HIV also disproportionately affects motivation to improve health behaviors and self-care in a variety communities of color. Despite only comprising 12.6% of the of clinical settings and populations. Games can attract and US population, nearly 45% of all new HIV infections occur maintain attention, a key component for effective behavior among African Americans. The use of antiretroviral medications change. Compelling interactive phone-based games can expose to reduce the risk of acquiring HIV infection (pre-exposure players to essential health-related content thousands of times prophylaxis, PrEP) is an efficacious and promising new and also give players unlimited opportunities to rehearse new prevention strategy [1,2]. There have been significant advances skills and receive personalized feedback on health choices made regarding PrEP including the definitive demonstration that PrEP within the game [28-30]. Games have been shown to be reduces HIV acquisition. Despite promising data, the practical efficacious in promoting fitness, improving weight management, implementation of PrEP is challenging [3-10]. Unfortunately, and improving safer sex skills [27,28,30,31]. For example, an individuals who are often at the highest risk of HIV infection HIV and AIDS prevention computer game called Life Challenge and eligible for PrEP come from populations that historically was developed by the New York State Department of Health have been underserved by health care [11,12]. Therefore, to enhance safer sex negotiation by adolescents and young engaging diverse persons on PrEP in care is challenging, and adults. The game showed significant improvement in reinforcement and support for patients and doctors is required self-efficacy for partner negotiation and condom skills for those [11,13-15]. Behavioral Interventions promoting adherence to who started with the least self-efficacy [30]. Two pregnancy comprehensive PrEP treatment and healthy sexual behaviors prevention games, The Baby Game and Romance, designed for will need to be tailored to diverse, underserved, and at-risk sexually active young adults, showed trends in improving populations and will need to reinforce the clinician-patient knowledge and attitudes about parenting and unprotected sexual relationship. behaviors [29]. Video games have also been applied to improve In addition, the behavioral interventions accompanying PrEP self-management skills and healthy behaviors in those living need to be scalable, cost-effective, and easily integrated into with asthma, diabetes, and cancer [32-36]. For example, a video clinical settings [2,16]. Without these necessary components, game named Re-Mission (tested with adolescents and young integration of behavioral interventions into clinical settings adults aged 13-29 years) was designed as an action-adventure cannot be realistically sustained. Utilizing gaming technology in which the main character shoots cancer-causing agents in the to deliver behavioral interventions for young men who have bloodstream. In a randomized control study, 375 male and sex with men (YMSM) can improve intrinsic motivation and female participants who played Re-Mission had significantly information and build behavioral skills for adherence. The use improved adherence to trimethoprim-sulfamethoxazole of an intervention that utilizes gaming technology is particularly (TMP/SMX; P=.01) and 6-mercaptopurine (P=.002) after an compelling for use with younger adults, as this age group is at average of only 10.7 hours of play. Adherence to TMP/SMX the highest risk of acquiring HIV and this age group has most by those playing Re-Mission was 19% greater than those in the actively inquired about PrEP in clinical settings. In addition, control group. Self-efficacy (P=.01) and knowledge (P=.03) 72% of young male adults in the United States say they play also increased [35,36]. Thus, appealing interactive games can video games often or sometimes [17]. Gaming technology is target information, motivation, and skills for medical care and also popular among minority men who have sex with men have led to a broad spectrum of desirable health outcomes (MSM), the subgroup most at risk for acquiring HIV. In the including increases in knowledge, attitude changes, and past, gaming was mistakenly identified as a primarily adolescent increased medication adherence [27,31,37-39]. and heterosexually dominated activity, but current data support Gaps in Literature that gaming is actually quite diverse [18]. MSM gamers, referred to as gaymers in pop culture and mainstream articles, are highly Despite the promise and popularity of digital games, there is a represented on the web and increasingly shape the market paucity of interventions or publications related to gaming for [19-21]. In addition, within the United States, African Americans persons on PrEP [40]. Relatedly, there are games in development aged 18 to 35 years represent the most active and fastest growing for YMSM either living with HIV or at risk for HIV [41-45]. user group of mobile phones [22,23], and more than half of the For example, our research group has developed a gaming http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 2 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al intervention to improve antiretroviral treatment (ART) aims for continuous design testing and adaptation based on adherence for youth and young adults living with HIV that continuous feedback [53]. informs the development of this game [40]. LeGrand et al have Sample and Recruitment published a description of the development phase of a game Males aged between 18 and 35 years were eligible for entitled Epic Allies. Epic Allies is designed to improve ART enrollment in the study according to the following criteria: (1) uptake, engagement in care, and adherence among HIV positive English-speaking, (2) currently taking PrEP, (3) reported having YMSM and transgender women who have sex with men. While sex with other men, and (4) able to give consent and not playing Epic Allies, users can earn medals and tokens for taking impaired by cognitive or medical limitations as per clinical medications and reading health-related studies. [42]. Another assessment. Those who did not meet the abovementioned intervention called PlayForward aims to reduce the risk for HIV inclusion criteria were excluded. We recruited 20 YMSM for among at-risk, ethnic, and racial minority adolescents. This qualitative interviews to guide game development after tablet-based game provides an interactive world using an avatar institutional review board’s (IRB) approval. Subjects were from where players face challenges such as peer pressure to drink a convenience sample recruited from a PrEP clinic in Jackson, alcohol or engage in other risky sexual behaviors [43]. A mobile Mississippi, between October 2016 and June 2017. Subjects phone–optimized intervention entitled healthMpowerment is were approached by research staff with an IRB-approved flyer, designed to reduce sexual risk behaviors among YMSM. In this and written consent was obtained upon meeting with study staff intervention, YMSM can acquire reputation points through for the qualitative interview. Overall, 20 subjects were reading information about HIV, playing sexually transmitted approached over the course of the interviews, and all of them infection (STI)–related games, and through positive interactions consented and completed the interview. Subjects were recruited with other users. Despite the promise and popularity of digital until data saturation was achieved, and a relative balance in the games, there are no published or presented abstracts related to sample was achieved based on age greater than 26 years versus gaming for persons on PrEP that we could find. younger. The mean age of participants was 26 years (range: This Study 18-35 years; 11 out of the 20 were younger than 26 years). A We developed a gaming intervention to improve adherence to majority of the participants (17/20, 85%) identified as African PrEP for YMSM aged 18 to 35 years. This intervention American, 100% (20/20) identified as MSM, 70% (13/20) integrates a smart pill bottle cap (that measures adherence) with completed 12th grade, 75% (15/20) had been taking PrEP longer an iPhone game. The gaming intervention was informed by the than 6 months, 75% (15/20) reported missing a dose of PrEP information-motivation-behavioral skills (IMB) theory of in the previous week, 45% (9/20) reported missing 3 doses or learning. The IMB model, consistent with social learning theory, more in the previous week, and 75% (5/20) had been taking is broadly applicable and can be used to guide game PrEP for 6 months or longer. development and create theoretically consistent gaming content Procedures [46-50]. The iPhone gaming app was designed for participants The study was approved by the hospital’s IRB, and participant to experience absorbing action-oriented adventures that increase consent and interviews were conducted in a private room located information about their health (eg, knowledge about PrEP and in a PrEP clinic in Jackson, Mississippi. Interviews were HIV prevention and adherence), improve motivation (eg, action conducted by 1 of the 2 MDs (psychiatrists) with support from figures experience health benefits of adherence to PrEP), and a trained research assistant, and subjects were reimbursed US build skills (action figures interact with clinicians at $50 per survey (for a total of US $150) for their time. The appointments, take medications as prescribed, and practice safe psychiatrists who conducted the interviews did not provide sex; see Multimedia Appendices 1-13). Adherence (measured medical or clinical services in the HIV clinic. Interviews lasted by the smart pill bottle cap) and game-related text messages are between 45 and 60 min and were digitally recorded. As we integrated into the gaming intervention. Multiple reviews have adapted our gaming intervention from games that were already demonstrated that behavioral interventions shown to be most developed (Dr. Nano X and BattleViro), the system and the efficacious are those tailored for the target population and framework (eg, code, database, and design) were already in preceded by formative research to inform intervention place at the beginning of the project. Adaptations to the game development [51,52]. The aim of this study was to describe the occurred as themes emerged from the interviews [41]. Biweekly development of this iPhone gaming app entitled ViralCombat. meetings were held with the programmers to discuss all adaptations, including changes to content, game graphics Methods framework, and game messaging. Gaming App Development Adaptation of the Information-Motivation-Behavioral Development of ViralCombat was accomplished using iterative Skills Adherence Gaming Intervention and collaborative procedures to integrate the clinical experiences The IMB gaming app for persons on PrEP, entitled ViralCombat, of YMSM taking PrEP, academic researchers, and technology was adapted from the popular Mission Critical Studios game partners. Game development was guided by qualitative entitled Dr. Nano X as well as our previously developed game interviews with a group of MSM aged between 18 and 35 years for persons on ART entitled BattleViro [40,41]. Dr. Nano X is taking PrEP. Guided by the principles of agile software a 5-star-rated mobile game (the highest rating possible) in the development [53], the qualitative interviews and the game and iTunes app store and is available on both Android and iPhone. app programming were synergistic. Agile software development http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 3 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al The ART adherence game, named BattleViro, has been storyboard of the game and completed interviews. When the previously described in the Journal of Medical Internet Research iPhone version became available, 9 participants were given the [41]. We worked directly with the development team at Mission game on an iPhone, and their feedback was elicited through an Critical Studios to develop ViralCombat using Dr. Nano X and interview. Therefore, qualitative feedback was received from BattleViro as a basic framework. Adapting our game to promote all 20 participants. The interview guide consisted of focused PrEP adherence from already existing games greatly decreased but open-ended questions aimed at maximizing participant the cost of the project. Characters, actions, and IMB messaging responses (see Textbox 1). Participants were asked about about PrEP were built specifically for ViralCombat; however, information relevant to medication adherence, motivating factors we were able to reuse backgrounds, mechanisms of game play to adherence, and behavioral skills needed for adherence. The and controls, and many sound effects from Dr. Nano X and IMB model guided interview content, and participants were BattleViro [54,55]. ViralCombat game levels are distinct from also queried about their general gaming experience and their those in BattleViro, and they include organ systems such as the reactions to the storyboard and gaming content. penis, anus, and mouth. Information Needed for Adherence We worked iteratively with youth living with HIV and Mission Participants were asked about knowledge and information that Critical Studios to create the app. The game starts with a influences their adherence to PrEP and engagement in medical 45-second narrative movie that explains the storyline and game appointments. Questions included: objectives. The player is told by the narrator, in a deep and What type of information from doctors or friends dramatic voice, “you have been chosen, due to your smart makes it easier to take PrEP? decisions and healthy choices, to be cloned and shrunken in order to enter your own body to destroy attacking viruses and What information makes it easier to come to PrEP infections.” The narrator emphasizes that “in order to acquire related appointments? ammunition and strength, you must take you medication in real This part of the interview aimed to understand the specific life and also pick up pills during play.” Players are given a knowledge about HIV and PrEP that promotes adherence tutorial on game actions and can also design their individual behaviors. For example, some probes focused on how side and diverse characters. As players successfully battle HIV, effects and other health-related information can influence engage with providers, and take medication, they move to new, adherence to medication and care (for more examples, see distinctive levels (arterial system, penis, anus, and mouth). Textbox 1). Messages from the doctors, nurses, and friends encourage and Motivation for Adherence provide clues during difficult twists and turns in the battle. Answering quiz questions from clinician avatars allows each Participants were queried about motivational issues related to player to earn strength and points; wrong answers are corrected adherence to PrEP with probes such as: and explained. Players find medication, strength, and points by I would like to hear about what you think the serious acting on positive suggestions. During each mission, the player’s issues are surrounding PrEP and taking medications score (pill count and health) is shown. All character control and to prevent HIV, gaming is done by touch screen technology on the phone; no What are the things that make it hard to take PrEP? additional accessories are needed for play. Throughout the game, the terms “HIV” and “PrEP” are seen on the screen, but they This part of the interview was dedicated to understanding both are never part of an audio feature, so stigmatizing information personal and social motivations for adherence to PrEP. Queries cannot be overheard by another person. The game-related text were focused on the positive and negative attitudes toward messages have gaming graphics, similar to other apps and taking PrEP, perceived negative effects of nonadherence to games, and the app uses push notifications to engage gamers PrEP, and the individual’s perceptions of social support from in play. If players were less than 90% adherent during the week, significant others, family, friends, and medical care providers phrases such as “Missing you in Combat” and “Get back in the (for more examples, see Textbox 1). game” are texted to their phones. Congratulatory short message Behavioral Skills for Adherence service (SMS) text messages such as “Great job in battle” and “You are fighting off virus well” are sent for greater than 90% Participants were also asked about their ability to perform adherence (see Multimedia Appendix 2). Throughout gaming, necessary adherence and HIV preventative tasks and their the mission stays the same: kill the virus and build strength perceived self-efficacy for these tasks. Questions included: through taking medicine, learning information, improving What are the ways that you stay safe from HIV? motivation, and engaging with healthy characters to improve What are the ways that you remember to take PrEP adherence to PrEP and build HIV preventative skills. and remember your PrEP related appointments? Interview Topics What events in your life make it harder to remember Interviews with YMSM taking PrEP-guided game development to take PrEP? Or remember your appointments? were conducted. A total of 11 participants were shown the http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 4 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Textbox 1. Qualitative interview guide based on the information-motivation-behavioral (IMB) skills model. Information What knowledge or information about HIV and pre-exposure prophylaxis (PrEP) is helpful to know? What knowledge or information helps you to take PrEP daily? Does knowing about side effects change decision making around taking PrEP? Motivation What are the main issues in coming for PrEP related medical appointments? What are the things that make it hard to take PrEP? What are the attitudes or feelings that people like you have that make it harder to take PrEP? Or easier to take PrEP? How do partners, your family, and your community play a role in adherence to PrEP related care? Behavioral skills Do you use alarms, your phone, or reminders to remember to take PrEP? What do you do if you miss a dose of PrEP? What are the strategies for adherence to PrEP over time and across different situations? Are there things that you do such as eating, or avoiding certain substances, that make taking PrEP easier? General gaming attitudes What is your reaction to getting some PrEP related and HIV related information and skills in a game? Do you ever play games that teach you facts or in which you learn something? Do you go online or use your phone to learn information about your health? Have you ever played a health-related game before on your phone or at a computer? Reactions to ViralCombat What did you like and not like about the game? What do you think this activity is trying to teach you? How much did the material look like the other games that you play? How could this activity or content be improved for others like you? Now that you have seen this game, would you want to play it? Before you came here today, did you ever find anything like this on a game on a phone or on a computer? Would you be worried about playing the game when others could see it? What would you say if someone asked you about the game? We also asked participants about strategies for General Gaming Attitudes self-reinforcement for adherence over time and across different Participants were also asked about their general attitudes and situations. We asked questions such as: experiences with games. Participants were asked questions such as: Do you consciously think about your PrEP medication schedule on a long-term basis? What games do you, or people you know, play on the What strategies have you used or developed to cellphone? remember to take PrEP or to go to your appointments What types of graphics, avatars, and rewards do you based on your activities? like? And what do you not like? This part of the interview aimed to assess perceived abilities How are games useful? Do you develop any skills and strategies to store, obtain, and self-cue the use of when you play games? medications despite challenges and across situations (for more These queries elicited descriptions of popular game activities examples, see Textbox 1). and attitudes about gaming. The responses were used to make the format and game mechanics of ViralCombat engaging and immersive (for more examples, see Textbox 1). http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 5 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al 3=“Mostly satisfied”; 2=“Indifferent or mildly dissatisfied”; ViralCombat Storyboard and iPhone Game and 1=“Quite dissatisfied”) [56]. We did not calculate an alpha Participants were asked for feedback about the storyboard or coefficient for this sample because of the small number of the iPhone game (once the mobile game was ready) with the participants completing the CSQ (n=9). In other studies, the probes such as: internal consistency of the CSQ-8 is high, with alpha coefficients What was the main point of this activity? ranging from .84 to .93 for the CSQ [58]. The SEF contains 13 items that assess the feasibility and perceived utility of activities What could you learn from this activity? in the game. For example, the SEF states: “I will be able to Would you recommend this type of game to your apply what I learned from this game in my life” (for which the friends? response options are 1=“Strongly agree”; 2=“Agree”; What is your reaction to having some HIV and PrEP 3=“Disagree”; and 4=“Strongly disagree”) [57]. As the SEF related information and skills in an iPhone game? asks about specific the utility of separate elements of the After the first version of the game was developed on the iPhone, intervention, and not about singular constructs, alpha coefficients participants were asked additional and modified probes such for the SEF are not commonly calculated. as: Data Analysis Is the game easy to navigate and easy to understand? Qualitative Data Did any part of the game not work? Trained research assistants transcribed verbatim the digital audio Are there other topics that the game should cover that recordings of each interview. Then, the MD- or PhD-level it does not? research team member reviewed the transcripts with the digital Answers to these questions guided the iterative development recording for accuracy. Qualitative data analysis followed the of the game levels, actions, characters, and graphics (for more tenets of thematic analysis, which consisted of sequential steps examples, see Textbox 1). [59,60], and interviews continued until data saturation was achieved. The research team familiarized themselves with the Medication Adherence Monitoring Tracking and data, reviewing each transcription. Next, the research team met Game-Related Text Messages weekly and generated a list of codes as they emerged. The team Participants were also asked about the electronic pill monitoring generated a thematic table of the analyses and checked the extent organizers and adherence-related text messages. We queried to which the emerging themes reflected the coded data [59,61]. participants about the smart pill bottle cap that can electronically The team grouped the themes under the general categories of monitor, measure, and securely relay adherence pill bottle the interview guide (ART information, ART motivation, ART openings to our research team. Participants were asked about behavioral skills, general game attitudes, and reactions to the use of reminder messages with a game-related graphic. ViralCombat). Themes were examined in their relation to Feedback was elicited about game-related messages if players perceived utility of the game and for factors that would improve missed a dose using texted phrases such as “Missing you in or detract from the game’s impact. Team discussion and Combat” and “Get in the game.” Feedback was also received interviews continued until discrepancies were resolved. about SMS text messages if doses are taken on time such as “Great job in battle” and “You are fighting off virus well!” (see Quantitative Data Multimedia Appendix 2). Participant responses on the CSQ and SEF were entered into an Excel file, and responses were verified with a second entry. Quantitative Feasibility and Acceptability Data Categorical response frequencies were calculated for each item The game was developed iteratively. A total of 11 participants of both scales. General acceptability of the intervention is were shown the storyboard of the game for approximately 30 illustrated using individual items from the scales. CSQ items min; qualitative feedback was elicited, and game development are reported using the proportion of participants endorsing on the iPhone occurred. After the development of the iPhone satisfaction with the intervention (response options “Very version of ViralCombat, 9 of the 20 participants played the satisfied” and “Mostly satisfied” were combined). SEF items game for 45 to 50 min with the interviewer in the room (see are reported using the proportion endorsing “agreement” with Multimedia Appendices 1-13). These 9 participants were shown feasibility and utility of the game (response options “Strongly each of the game levels on the phone by the interviewer and agree” and “Agree” were combined). played each level. After playing the game, these 9 participants completed qualitative interviews, and then, written or Results quantitative feedback was obtained. Quantitative feedback was collected from these 9 participants using versions of the Client Reactions to ViralCombat Storyboard and iPhone Service Questionnaire (CSQ) and the session evaluation form Game (SEF) [56,57]. Both these instruments were developed to Interviews from both the storyboard and iPhone game revealed measure client satisfaction and perspectives on intervention a number of themes that guided game development. Participants aspects. The CSQ consists of 8 items that assess general desired informational game content that included new and satisfaction with the game. An example query from the CSQ is comprehensive details about PrEP, details about PrEP as it “In an overall, general sense, how satisfied are you with the relates to doctors’ visits, and general health information. game?” (for which the response options are 4=“Very satisfied”; http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 6 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Motivational themes that emerged were the desire for I think there should be facts in the game about other enhancement of future orientation; reinforcement of positive health stuff, about smoking and drinking on PrEP. influences from peers, partners, and friends; collaboration with Many participants also wanted more guidance through the levels. health care providers; decreasing stigma; and increasing personal For example, a 29-year-old white male participant stated: relevance of HIV prevention. Behavioral skills themes centered I would like better hints on each level on how to beat around self-efficacy and strategies for PrEP adherence and the level. medical care (see Textbox 2 for qualitative interview themes and resulting game adaptations based on the IMB model). An 18-year-old black male said (see Textbox 2): Textbox 2 highlights the barriers and facilitators to adherence Clues or hints when it gets hard would make this expressed by our participants and the corresponding gaming better. app action or message that was adapted to enhance facilitators Monitoring Pill Bottle Opening and Game-Related or challenge barriers. Textbox 2 also includes general gaming Text Messages attitudes that influenced the development of ViralCombat and We asked participants about the SMS text messages with gaming specific reactions to the ViralCombat storyboard and iPhone graphics and the use of a smart pill cap that measured adherence. game. In addition to the themes in Textbox 2, participants who During the interviews, we demonstrated how openings of the played the game on the phone said that important gaming pill bottle were measured wirelessly, and we showed participants characteristics included directly destroying and fighting off HIV sample adherence-informed SMS text messages. When looking in game play, earning health points by taking pills that looked at the smart pill cap, an 18-year-old black male participant like PrEP, a prologue or introduction with a dramatic voice-over, stated: and images about HIV and STIs that were relevant. Participants wanted levels that become increasingly difficult (for a sense of It’s cool how it links with game. accomplishment). Participants did not want HIV or PrEP in the It’s awesome that there is a bottle that knows what title of the game because of concerns about privacy and stigma you are doing. but wanted to fight graphics labeled “HIV” and wanted to see The feedback about the cap was extremely positive; however, the word PrEP during gaming. A 29-year-old black male a 19-year-old black male participant stated: participant said: The pill cap is OK, I don’t love how big it is. People I like that the organ systems are the penis and the can see it in my bookbag more. anus, it’s funny, but also realistic. It helped me learn about how infection with HIV happens. A 26-year-old white male described: A 30-year-old white male participant said: It would be better if it was a bit smaller, but I like that it can record when I take pills, that helps me. It was awesome to shoot HIV virus before it enters the body, and I like that HIV looked like it would Although 2 participants had negative remarks about the size of under a microscope. the pill bottle, 18 out of 20 participants responded they liked the cap design and did not think the size of the cap was an An 18-year-old black male stated: impediment to use. During interviews, participants were also I liked taking pills that look exactly like PrEP; it’s shown SMS text messages that corresponded to adherence data like my real-life. from the smart pill cap. Participants liked the proposed SMS A 21-year-old white male stated (see Textbox 2): text messages, and an 18-year-old black male described: It was cool that I am playing a game about These texts cue me to take my meds. preventing, that it was like tailored to me and my A 30-year-old black male stated: friends. I like the game pictures. I think my other friends who think about HIV would ...the texts made me smile and also I felt like they were like playing this. just for me. The music and sound is really awesome. A 35-year-old black male participant described: The game was iteratively changed as comments were received that indicated a need for alteration. For example, facts about The texts got me in the mood to play the game again. HIV prevention and the benefits of adherence to PrEP were Of the participants, 3 described that they wanted more variation made more sophisticated when multiple participants gave in the game-related texts: feedback such that they knew most of the information given in Seeing the same graphics again and again is boring. the game and that they wanted more detailed information about [35-year-old black male and a 19-year-old black male] side effects. Many participants also asked for information about substance use. A representative comment was from a 19-year-old An 18-year-old black male stated: black male who said: I would like more variety in the game texts. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 7 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Textbox 2. Qualitative interview themes and resulting game adaptations based on the information-motivation-behavioral skills (IMB) model. Information New and comprehensive details about pre-exposure prophylaxis (PrEP) and how PrEP prevents HIV Game includes complex and realistic information about PrEP. Participants fight off HIV in each organ. HIV is graphically represented. Facts about HIV and PrEP are imparted at every level. HIV is pictured. PrEP as it relates to doctors’ visits Terms and verbiage often used at PrEP-related doctor visits are used and defined in the game frequently. The importance of regular HIV testing and testing for other STIs is explained. General health information Participants learn about sexually transmitted infections that PrEP does not protect them from getting (gonorrhea, syphilis, herpes, genital warts, and human papillomavirus). Participants in the game receive messages about how exercise and healthy eating also affect health. Participants also receive messages about avoiding illicit substances and how illicit substances can increase risk behavior. Motivation Enhancement of future orientation Messages about staying healthy for family, friends, and children scroll through game. As gaming participant takes more pills and builds more health, they are able to move through levels, receive more artillery, and have more success staying healthy. Personal relevance of HIV Participants are shrunken down to enter into their own body to fight HIV. During game play, participants see how PrEP works to prevent HIV infection. Collaborating with health care providers Throughout the game, participants partner with doctors to advance to the next level, build strength, and collect artillery. Reinforce influences from peers, partners, and friends Scrolling messages remind gamers that staying healthy for partners, friends, and family is meaningful for themselves and for the loved ones in their lives. Decrease stigma Participants are empowered to kill HIV before it enters the body and gain points with each healthy decision. Adherence to PrEP is valued as healthy and smart decision-making. Behavioral skills Self-efficacy for PrEP adherence and PrEP-related medical care Solving problems and collecting pills or swallowing pills in the game leads to more points, which leads to more strength, more health, and more artillery. This leads to more game play. Perseverance throughout levels leads to success in the game. Strategies for medication adherence and self-care Scrolling messages encourage the participant to use PrEP, schedule routine doctors’ appointments, and ask providers or doctors questions about topics relevant to HIV prevention. General gaming attitudes Desire for games with levels, sound effects, and colorful graphics. Ability to earn points in the game and choose avatars Levels or organ systems become increasingly difficult (for a sense of accomplishment). Background music, sound effects, and dramatic voice-overs are included. Colorful graphics are included and change often. Choice of avatars is available. Participants earn points in the game by swallowing pills. Reactions to ViralCombat Desire for game action that is realistic with relevant information about PrEP and HIV prevention. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 8 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al Participants can directly destroy HIV in game play, and graphics look like PrEP and HIV. Participants improve health and gain points in the game by taking virtual PrEP pills. Participants liked progression through organ systems, with information about PrEP and HIV that is pertinent to that organ system. Textbox 2). Specifically, game play was made easier with Acceptability and Feasibility written messages and hints throughout each level on how to CSQ and SEF scores were available from participants who move forward. We also improved narrated instructions at the played the game on the iPhone for 45 to 50 min. The responses beginning of each level to assist players. General health facts were generally quite positive, 88% (8/9) of the participants were about smoking, side effects of PrEP, and how substances such satisfied with the activities in the game, 77% (7/9) learned a lot as drugs and alcohol can increase risky behavior were from this game, 88% (8/9) thought the game was well organized, incorporated into the game to increase perceived relevance. We 77% (7/9) felt game topics were interesting, 100% (9/9) felt also incorporated more detailed information about HIV and they would recommend the game to a friend, 77% (7/9) felt how PrEP works to improve learning and interest. We also game topics stimulated their interest in the material, 100% (9/9) included a condom quiz game and information about other STIs felt that game topics were relevant to their lives, and 66% (6/9) (see Multimedia Appendices 7, 8, and 11). To improve SMS felt they were able to do the activities in the game (see Table text messages, we included emojis and designed 5 different 1). The gaming intervention was improved based on the above game-related SMS text messages utilizing a larger variety of acceptability and feasibility feedback from the CSQ and SEF game graphics based on participant feedback. and also on the feedback from the qualitative interviews (see Table 1. iPhone game acceptability and feasibility scores (N=9). Questionnaire or form Participants endorsing statement, n (%) Client Service Questionnaire How would you rate the quality of the game? 8 (88) Did you get desired information from the game? 6 (66) To what extent does the game’s content meet your needs? 7 (77) If a friend were interested in a similar program, would you recommend our game to him or her? 9 (100) How satisfied are you with the amount of information you have received in the game? 7 (77) Has the information you received helped you to deal more effectively with issues important to you? 8 (88) In an overall, general sense, how satisfied are you with the game? 8 (88) Would you come back to the game again? 9 (100) Session evaluation form I learned a lot from the game. 7 (77) I will be able to apply what I learned from the game in my life. 6 (66) I was able to do the activities in the game. 8 (88) The game was well organized. 7 (77) The topic of the game was interesting. 7 (77) The presentation of the information stimulated my interest in the material. 9 (100) The topics of the game were relevant to my life. 8 (88) The game was enjoyable. 8 (88) I would recommend the game to others. 9 (100) I felt comfortable during game play. 9 (100) Proportion of participants that endorsed “Very satisfied” and “Mostly satisfied.” Proportion of participants that endorsed “Strongly agree” and “Agree.” http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 9 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al this study repeatedly expressed having access to, and familiarity Discussion with, iPhones. This widespread use of iPhones facilitates the uptake of gaming apps in clinical populations. Therefore, mobile Principal Findings technologies such as mobile phone games and apps have a great In this project, we utilized in-depth interviewing, focused by potential to enhance medical care and prevention interventions social learning theory (IMB), to create an iPhone gaming for populations who are disproportionately affected by HIV and intervention to measure and improve treatment PrEP adherence other STIs. and decrease HIV risk for YMSM [46-48,53,62]. A number of Limitations themes emerged through qualitative interviews with young men that informed game development. We found that YMSM desired Findings should be interpreted in light of study limitations. First, informational game content that included comprehensive details our participants were recruited from a PrEP clinic in Jackson, about how HIV is transmitted, PrEP-related doctors’ visits, side Mississippi. This clinic may not be representative of all PrEP effects of PrEP, and general health information. Motivational clinics in the United States or internationally. Therefore, the themes or findings that emerged were the desire for enhancement generalizability of the data collected to inform the development of future orientation; the need for reinforcement of positive of the app is unknown and may be limited. Second, this study influences from peers, partners, and friends; and the promotion focused on individual PrEP user perspectives. It may be equally of collaboration with health care providers. Motivational themes important to integrate the perspectives of clinicians, friends, or also included decreasing stigma and increasing personal partners into the game. In the future, including friends and social relevance of HIV prevention. Behavioral skills themes or networks into gaming prevention programs could be novel and findings centered around self-efficacy and strategies for PrEP effective. Perspectives of partners, friends, and clinicians could medication and appointment adherence including regular HIV also lead to a more robust understanding of barriers and and STI testing. facilitators to adherence to PrEP and PrEP-related medical care. Therefore, future research could examine the utility of Using the IMB theory in the development of this game ensured integrating feedback from clinicians and friends into the gaming that the intervention was informed by decades of prevention app. Finally, this app was developed for the iPhone. research. This study demonstrates that qualitative assessment, Development of the app for Android devices could allow for social learning theory, and agile software development can greater availability of the game and could be a forthcoming step complement each other and are important components to the in the future phases of research. development of a tailored and clinically relevant app. Participant data were used throughout the development of the game and Conclusions informed the informational, motivational, and behavioral This study is a significant step in the development and testing skill-building components of the game. Using a storyboard of an iPhone gaming app to promote adherence to PrEP and provided the research team with opportunities to share concept PrEP-related medical care. The long-term goal of this research models with participants early on in the design process and program is to test ViralCombat in a randomized trial and gather feedback with respect to necessary modifications. Sharing examine if the game is effective in changing PrEP-related the iPhone game with participants as it was developed also attitudes and adherence-related behaviors. If the results appear allowed for necessary, incremental improvements. YMSM at promising, the research team can distribute the technology risk of HIV infection provided key qualitative insights with procedures for the intervention to relevant and interested clinics, respect to the content and design and process of the game. community-based organizations, the Centers for AIDS Research, Tailored games that are informed by those who will use them and AIDS Trials Networks. The app could also be made have more potential for effective integration and uptake in available on iTunes and Google Play (Android) for a nominal clinical settings [41]. fee. Although iPhone games are pervasive in popular culture, no There are many advantages to using newer interactive other gaming apps have been developed for YMSM on PrEP. technology to improve adherence rather than traditional Findings of this study highlight several important barriers and face-to-face counseling, including scalability, efficiency, and facilitators to PREP adherence for YMSM. Mobile interventions cost-effectiveness. As electronic games are highly appealing to have the potential to reinforce skills learned in the clinic and young men [25], they are a natural opportunity to deliver health require fewer resources to deliver patient-centered, education during leisure time and outside of the clinic evidence-based interventions [63]. Furthermore, apps and mobile [25-27,52]. Games can attract and maintain attention, which is phone games have the potential to engage YMSM in a key component for effective behavior change. Compelling interventions, who otherwise may not be willing or able to interactive games can expose players to essential health-related participate in intervention programs. content thousands of times and also give players unlimited Gaming and mobile apps also have the potential to advance the opportunities to rehearse new skills and receive personalized delivery of information and promote healthy decision-making feedback on health choices made within the game [28,35]. We in disproportionately affected populations, including minority are not aware of other adherence interventions that integrate men who often have less access to medical care and support medication adherence monitoring technology, SMS text [60]. National data from the Pew Research Center indicate that messaging, and a theoretically informed game to improve younger, ethnic and racial minority populations use mobile information, motivation, and behavioral skills for PrEP phones frequently [64]. The adolescents and young adults in adherence. An intervention with these components may http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 10 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al empower and engage YMSM, aid clinics, and result in improvements in health. Acknowledgments This publication was made possible with help from the Providence-Boston Center for AIDS Research (P30 AI 042853). The project described was supported by grant number R34MH104068 (MPI: LW, LKB) from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health. Conflicts of Interest LM is a member of the Gilead Sciences Advisory Board and receives compensation for consulting from Gilead Sciences, Inc. No competing financial interests exist for the remaining authors. Multimedia Appendix 1 ViralCombat main menu graphic. [PDF File (Adobe PDF File), 66KB-Multimedia Appendix 1] Multimedia Appendix 2 Example of a short message service text message to the participants. [PDF File (Adobe PDF File), 62KB-Multimedia Appendix 2] Multimedia Appendix 3 ViralCombat game menu. [PDF File (Adobe PDF File), 37KB-Multimedia Appendix 3] Multimedia Appendix 4 Short narrative movie at the beginning of the game. [PDF File (Adobe PDF File), 57KB-Multimedia Appendix 4] Multimedia Appendix 5 Players can design and individualize their game character. [PDF File (Adobe PDF File), 47KB-Multimedia Appendix 5] Multimedia Appendix 6 Players are shrunken down to be able to enter the body to fight off HIV. [PDF File (Adobe PDF File), 29KB-Multimedia Appendix 6] Multimedia Appendix 7 Answering questions with allied doctors and building knowledge help each player successfully move to the next level or area of the body. Example of questions answered incorrectly. [PDF File (Adobe PDF File), 46KB-Multimedia Appendix 7] Multimedia Appendix 8 Answering questions with allied doctors and building knowledge help each player successfully move to the next level or area of the body. Example of questions answered correctly. [PDF File (Adobe PDF File), 42KB-Multimedia Appendix 8] Multimedia Appendix 9 Example of a player gaining strength in the anus level by collecting health pills and condoms. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 11 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Whiteley et al [PDF File (Adobe PDF File), 23KB-Multimedia Appendix 9] Multimedia Appendix 10 As players travel through the bloodstream, they must fight off viruses and gain health pills. [PDF File (Adobe PDF File), 51KB-Multimedia Appendix 10] Multimedia Appendix 11 Throughout ViralCombat, players engage in various games in order to move on to the next level. In the Condom Sequence game, players must go through the correct sequence of steps for correctly using a condom. 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US Smartphone Use in 2015 URL: http://www.pewinternet.org/2015/04/01/us-smartphone-use-in-2015/ [accessed 2019-01-21] [WebCite Cache ID 75aq2AOok] Abbreviations ART: antiretroviral treatment CSQ: Client Service Questionnaire IMB: information-motivation-behavioral skills IRB: institutional review board MSM: men who have sex with men PrEP: pre-exposure prophylaxis SEF: session evaluation form SMS: short message service STI: sexually transmitted infection TMP/SMX: trimethoprim-sulfamethoxazole YMSM: young men who have sex with men Edited by G Eysenbach; submitted 23.08.18; peer-reviewed by J Vandenberg, L Hightow-Weidman; comments to author 12.10.18; revised version received 05.12.18; accepted 09.12.18; published 27.03.19 Please cite as: Whiteley L, Mena L, Craker LK, Healy MG, Brown LK Creating a Theoretically Grounded Gaming App to Increase Adherence to Pre-Exposure Prophylaxis: Lessons From the Development of the Viral Combat Mobile Phone Game JMIR Serious Games 2019;7(1):e11861 URL: http://games.jmir.org/2019/1/e11861/ doi: 10.2196/11861 PMID: 30916652 ©Laura Whiteley, Leandro Mena, Lacey K Craker, Meredith Garver Healy, Larry K Brown. Originally published in JMIR Serious Games (http://games.jmir.org), 27.03.2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on http://games.jmir.org, as well as this copyright and license information must be included. http://games.jmir.org/2019/1/e11861/ JMIR Serious Games 2019 | vol. 7 | iss. 1 | e11861 | p. 15 (page number not for citation purposes) XSL FO RenderX

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JMIR Serious Games – JMIR Publications

Published: Mar 27, 2019

Keywords: cell phone; HIV; young adult; sexual and gender minorities

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