Recent mHealth interventions to support medication adherence among HIV-positive men who have sex with men

Abstract

Purpose of Review

We describe recent mHealth interventions supporting antiretroviral (ART) medication adherence among HIV-positive men who have sex with men (MSM).

Recent Findings

Keyword searches (1/1/2016 to 5/13/2017) identified 721 citations. Seven publications reporting on six studies met inclusion criteria. Five studies focused on MSM. Interventions primarily employed text messaging (n=4), while two focused on smartphone apps and one on social media. Three studies measured intervention impact on adherence and found increased ART use intentions (n=1), self-reported adherence (n=1), and viral suppression (n=1, no control group). Other mHealth interventions for HIV-positive MSM focused on status disclosure and reducing sexual risk.

Summary

mHealth interventions to support ART adherence among MSM show acceptability, feasibility, and preliminary efficacy. No recent mHealth interventions for MSM measured impact on viral suppression compared to a control condition despite earlier (pre-2015) evidence for efficacy. Studies are underway that include multiple features designed to improve adherence within complex smartphone or internet-based platforms. Areas for future growth include overcoming measurement and engagement challenges, developing tools for coordinating patient and provider adherence data, testing combination interventions, and adapting efficacious interventions for new languages and geographic settings.

Introduction

Globally, gay, bisexual, and other men who have sex with men (MSM) are disproportionately impacted by HIV [1, 2*, 3]. MSM are estimated to account for 18 to 49% of all new HIV infections worldwide [4], with larger proportions in high-income countries such as the United States (US) (67% of all new diagnoses in 2014) [5]. Treatment with antiretroviral therapy (ART) to achieve viral suppression improves individual health [6] and prevents onward transmission [7, 8**, 9**, 10]. Sustained adherence to ART is critical for long-term viral suppression, but remains suboptimal among MSM, ranging from 16 to 74% across 12 countries [11]. In the US, only half of all HIV-diagnosed MSM are estimated to achieve viral suppression [12], with significantly lower rates documented among young MSM (6–7%) [13, 14].

Societal stigma and discrimination within health care systems impede access to quality HIV care for MSM and influence adherence and viral suppression [15–17]. Many MSM manage multiple adherence barriers (e.g. mental health, unstable housing) [16, 18, 19], with each factor increasing the chances of having a detectable viral load [16, 20**]. Despite clear need, few ART adherence interventions have focused explicitly on MSM [21*, 22]. Among 117 US-based ART adherence interventions published between 2007 and 2015, only two focused on MSM [21*].

Mobile health (mHealth) interventions – including text-message (SMS)-based and multi-component smartphone apps, mobile-optimized websites, and social media interventions – offer highly accessible and adaptable platforms to support medication adherence [23, 24, 25**]. The flexibility of mHealth interventions allows the delivery of tailored content for each user’s needs [23] and accessibility helps reduce some societal and structural barriers [26]. mHealth also offers strong capability for scalability and diffusion across geographic locations, including within resource-limited settings [27*].

mHealth tools have not yet been fully explored in support of ART adherence for MSM. A 2016 review of social media-based interventions found no interventions focused on supporting ART adherence among HIV-positive MSM [28**]. Similarly, a 2017 systematic review and meta-analysis of the impact of text messages reminders on HIV care compliance [29**] found only one HIV-positive MSM-focused intervention [30]. Given the rapid pace of technology development, this review aims to focus on HIV-positive MSM to identify recent interventions and highlight new contributions in the use of mHealth to support ART adherence.

Methods

We searched PubMed from 1/1/2016 to 5/13/2017 for English language publications, using combinations of keywords and MeSH terms: HIV, AIDS, antiretroviral, ART, therapy, medication, adherence, compliance, non-adheren*, technology, technology-based, SMS, text messag*, texting, online, internet, web, Web 2.0, social media, social networking, app*, application*, smartphone*, cell phone*, cellular phone*, mobile phone*, eHealth, mHealth, video conferenc*, videoconferenc*, Twitter, Grindr, Jack’d, Facebook, computeriz*, computer-based, virtual reality, VR, MSM, men who have sex with men, gay, homosexual, bisexual, LGBT*, sexual minorit*. Publications were excluded that did not include: 1) an intervention description, 2) an mHealth intervention component; 4) an ART adherence behavioral (e.g. self-reported medication taking, device recorded medication taking) or biomedical (e.g. viral load, viral suppression, drug levels) outcome; or 5) a focus on MSM populations or report including MSM sub-populations. Three authors reviewed citations and full texts were pulled for all citations noted as relevant by at least one reviewer. Of the 721 articles extracted, seven articles reporting on six interventions met inclusion criteria (Table 1).

Table 1.

mHealth antiretroviral medication adherence interventions for HIV-positive men who have sex with men, 2016 – 2017

Citation Study name	Population Sample size Location	Technology Study type	Intervention (I) Control (C)	Results
Herbst et al., 2017 [31*] Messages4 Men	Black & Latino MSM diagnosed >6 mo n=320 (age: 28% 18–29; 23% 30–39; 50% 40+) US	One-way SMS Pilot study	I: Single session, 3 brief messages to increase intentions for behavior change: 1 each focused on ART self-benefit & partner-benefit, 1 on condoms C: None	Some increased intentions for ART use & condom use. Detectable VL associated with reporting message content was new information. Of note: SMS content was tested on web platform, not actually sent to phones. 91% already on ART
Rana et al., 2016 [32**]	New-to-care or care/ART challenges PLHIV n=13/32 MSM (full sample mean age: 36) US	Two-way SMS + monthly phone call Pilot study	I: 6-mo of standard or user created SMS on daily ART, appointments, barriers to staying in care. User queries answered by SMS or call within 24 h (weekdays) or 48 h (weekend). Monthly call to adjust frequency of SMS based on user choice. C: None	BL to 6-mo FU: VS increased 56 to 78% (p=0.002). 79.1% of scheduled HIV care visits kept (range 0–100%). Qualitative exit interviews (n=20): high SMS acceptability, satisfaction with frequency, content, & helpfulness. Users appreciated combined SMS/human support. Of note: 2 participants ineligible due to no cell phone. No participants changed frequency of SMS during study, 3 changed SMS content. No sub-analyses reported for MSM
Ruan et al., 2017 [33*]	ART w/i past 3 mo PLHIV n=4/100 MSM (full sample mean age: 40.3) Hunan, China	Two-way SMS RCT	I: 6-mo of two-way SMS using an IMB-based 3-step adherence model. 124 SMS in 6 “modules” (e.g. greetings, ART reminders, HIV knowledge, humor, motivation). Mo 1–3: 5 SMS/week, mo 4–6: 3 SMS/week. ART SMS sent 30 min prior to scheduled dose, other SMS sent at 8PM C: SOC	I vs. C, BL to 6-mo FU: no difference in CD4; self-report ART adherence by VAS was 98.72% vs 93.11%, p=0.006); 96% satisfied/highly satisfied with I; 74% wanted to continue receiving SMS. Desired frequency of SMS: 1–2/week Of note: All SMS <70 Chinese characters, HIV-related terminology avoided. No sub-analyses reported for MSM. Only 1 MSM participant was randomized to the intervention arm.
Senn et al., 2017 [34**, 35*]	Black MSM, missed apt, break in care, <95% ART n=3 mentors; n=8 mentees (mean age: 40) US	Two-way SMS app (for Android) + peer support Design, develop, pilot study	I: For 1-mo mentors provide via SMS informational & motivational support about HIV; help mentees build skills to stay in care & take ART (based on IMB). Mentors’ protocol: respond to texts within 12 hours; contact at least every 3 days. C: None	Intervention was feasible & acceptable: 5/7 were satisfied/very satisfied. Mentees wanted more frequent contact; mentors & mentees wanted more personalized contact (e.g. introductory phone call). Social media was recommended as additional contact. No care outcomes reported. Of note: study cell phones were purchased for both mentors & mentees. 4 participants experienced technical/logistical problems with phone or app.
Tanner et al., 2016 [36**] weCare	Racially & ethnically diverse MSM, age 13–34 US	Health Educator + social media (Facebook), SMS, in-app IM Design & develop	I: CBPR-developed, based on SCT and Theory of Empowerment Education. Health Educator interacts in-person and via SMS, Facebook, and in-app IM based on participant preferences to provide: ART refill & daily med reminders, problem solve ART prescription & adherence barriers, applaud positive behaviors. C: NA	weCare scheduled to start late 2016. Dose will be measured by Health Educator recording participant interactions through a secure REDCap log. Of note: weCare covers full Continuum of Care – here we focus only on ART & VS. Health Educator will maintain profiles on Facebook, A4A/Radar, badoo, Grindr, Jack’d, & SCRUFF; will use BlueStacks App Player and Fake GPS software to operate apps from desktop to “appear” in catchment cities where participants live.
LeGrand et al., 2016 [25**] Epic Allies	MSM, age 20–28 n=3 focus groups (20 MSM); 7 MSM one-on-one usability sessions US	App for iPhone, Android Design, develop, usability testing	I: IMB theory-informed ART adherence app utilizes game mechanics, social networking features, personalization (e.g. editable profile & avatar), tailored feedback messages, functional ART support (e.g. editable medication alarm, daily medication tracker), & privacy features. C: NA	26/27 participants identified as black/African American. Participants preferred an adherence app that was informational, interactive, social & customizable. In usability testing, app was easy to understand & navigate, & was rated highly. Of note: Multi-feature app where each feature is linked to components of IMB model. Epic Allies is currently completing a 5-site RCT implemented within the US ATN.

ART: antiretroviral therapy; ATN: U.S. Adolescent Medicine Trials Network for HIV Interventions; B: baseline; C: control; FU: follow-up; IM: instant messages; IMB: Information-Motivation-Behavioral Skills; I: intervention; min: minutes; mo: month; MSM: men who have sex with men; PLHIV: people living with HIV; RCT: randomized controlled trial; SMS: text messages; SOC: Standard of Care; US: United States; VAS: Visual Analog Scale; VS: viral suppression

Recent ART mHealth adherence interventions tailored for or inclusive of MSM

For core mHealth components, most interventions used text messaging, including three pilot studies, one randomized controlled trial (RCT) [31*, 32**, 33*, 34**], and one planned intervention that will use social media and text messages [36**]. One article reported on the development and usability testing of a stand-alone smartphone app [25**]. Studies were based in the US (n=5) and China (n=1) [33*]. Three US-based studies focused on Black or Black and Latino MSM [31*, 34**, 36**], and one on general MSM (96% Black) [25**]. The average participant age across four studies was over 35 years old, while two studies explicitly focused on adolescents and young adults [25**, 36**]. Three interventions reported being informed by the Information Motivation and Behavioral Skills model (IMB) [25**, 33*, 34**] while one utilized Social Cognitive Theory (SCT) in conjunction with the Theory of Empowerment Education [36**]. Studies that measured outcomes related to ART or viral suppression found moderate increase in intentions to use ART (albeit among individuals already on ART) [31*], increase in viral suppression [32**], and higher self-reported adherence (intervention vs. control at 6-month follow-up, 98.72% vs 93.11%, p=0.006) [33*]. Below we highlight a few findings and novel features from these interventions.

Messages4Men tested brief, one-way messages in a single-session pilot study that aimed to increase intentions for behavior change among HIV-positive and HIV-negative Black and Latino MSM in three US cities [31*]. Eligible HIV-positive men were: 18 and older, diagnosed for at least six months, and not currently in another HIV-related study. Messages for HIV-positive MSM focused on the benefits of ART adherence to oneself and one’s partner and condom use. No overall association between viewing the messages and increased intention for ART use was found. Among participants with detectable viral load, exposure to messages about benefits of ART to oneself was associated with reporting messages provided new information (AOR = 2.32; 95% CI = 1.04–5.26) and exposure to messages about ART benefit to one’s partner was associated with intentions for ART use (AOR = 7.69; 95% CI = 1.01–50.0). These findings highlight the importance of message tailoring and targeting for achieving specific desired impact among different subpopulations of MSM - in particular continuing to emphasize the benefits of adherence for both individual health as well as its importance for reducing transmission.

Two interventions combined two-way – or bidirectional – text messaging with another intervention component. The first, by Rana and colleagues, included 32 people living with HIV in the US who were either new to care, had experienced a break in care of a year or more, or who were considered by their provider to be at-risk for ART or appointment non-adherence (14/32 had detectable viral load at baseline, 13/32 identified as MSM) [32**]. Participants received six months of text messages about adherence and HIV care. At enrollment, participants were prompted to identify their own barriers and facilitators to care or choose from pre-selected barriers and facilitators adapted from the US CDC’s Medical Monitoring Project. Study staff called once per month to discuss and adjust (if needed) frequency and content of text messages. Comparing baseline to follow-up, the proportion of virally suppressed participants increased from 56% to 78% (p = 0.002).

The second intervention, by Senn and colleagues, described formative work [35*], development, and pilot testing [34**] of a text messaging plus peer support intervention to improve retention in care and adherence for Black MSM in the US. Peer mentors – themselves HIV-positive Black MSM – received a two-hour training on information and skills related to ART and HIV care and how to respond to participants (“mentees”) in nonjudgmental, motivational ways. Participants were assisted in sending their first message to peer mentors at study enrollment. For one month, mentors communicated with mentees via text message. Mentors were asked to respond to texts within 12 hours and to make contact with mentees at least every three days. Five out of seven participants were satisfied/very satisfied with the intervention. Mentees wanted more frequent contact while both mentors and mentees wanted more personalized contact (e.g. an introductory phone call). Social media was recommended as additional form of contact that could be used. No ART outcomes were reported [34**].

Two manuscripts reported on the development and/or usability testing of two adherence interventions for young MSM [25**, 36**]. Epic Allies is a theory-informed smartphone app designed to support engagement in care, ART initiation and adherence, and viral suppression [25**]. The app utilizes game mechanics, social networking features, personalization (e.g. editable profile and avatar), weekly tailored feedback messages, and functional ART support (e.g. medication adherence tracker and reminders). Epic Allies was developed in three phases including initial conceptualization, theory-based design and prototype development; three focus groups with 20 MSM (age 20 – 28); and usability testing with seven MSM (age 20 – 28) [25**]. Based on feedback through development and usability testing, the app was further refined and is currently undergoing a five-site randomized controlled trial through the US Adolescent Medicine Trials Network for HIV/AIDS Interventions [37].

Lastly, Tanner and colleagues describe the design and development of weCare – an intervention for racially and ethnically diverse US MSM, age 13–34 [36**]. weCare was developed using processes of community-based participatory research and is based on SCT and the Theory of Empowerment Education. Although weCare covers the full HIV Continuum of Care, here we focus only on ART and virologic outcomes. A Health Educator interacts in-person and via text message, Facebook, and in-app instant messaging to provide participants with reminders, information, and problem solving regarding ART prescriptions and refills and adherence. Implementation and evaluation of weCare was scheduled to start in late 2016 [36**].

What core features should be included in an ART adherence mHealth intervention for MSM?

Above we described recently published mHealth interventions identified through systematic searches. We now turn toward synthesizing key features from these interventions in the context of previous and future mHealth adherence interventions for MSM.

Text messages are generally shown to be effective at improving medication adherence across a variety of populations and settings [29**, 38**] (with some exceptions [39]). Further, short weekly text messages have been shown to perform better than daily messages in reducing non-adherence [30, 40, 41]. All interventions identified in this review included at least some component of text message reminders, reflecting this as a current core feature in adherence support interventions. A 2017 meta-analysis of ART adherence interventions found multiple interventions achieved better results than single interventions [38**]. As suggested by the studies reviewed above, interventions testing text messages in combination with other features (e.g. social media contact, app-based self-monitoring) show promise for increasing the effectiveness of messages alone.

Indeed, MSM participants request [34**] and appreciate [32**] enhancements beyond text messages that focus on social support and connection with others. In focus groups about HIV-related app preferences with stimulant-using adult MSM, participants requested social networking features, information about local resources, connection to their medical chart, and HIV-related news [42**]. These requests for information and connection are echoed in focus groups with young MSM along with preferences for information that is presented succinctly [43], customizable app features [25**], personalized reminders and accountability for medication taking behaviors [44*], and information on both HIV and general health and wellness [43, 44*]. Anonymity and privacy are also consistently stressed features – though not inherent barriers to using mHealth HIV interventions [35*, 43, 44*].

Thus there is interest, public health need, and scientific rationale for multi-component, complex mHealth interventions to support ART adherence among MSM. Interventions should be responsive to current best practices for mHealth-supported ART adherence and tailored to men’s expressed needs and preferences. Intervention developers may want to consider incorporating gamification to improve engagement [45, 46] and dynamic tailoring based on frequent assessments – features that effectively promote ART adherence [30, 47]. Several interventions are underway that do this for MSM. Thrive with Me is a theoretically-based (IMB model), multi-component ART adherence intervention for MSM age 18 and older (majority substance users) that includes asynchronous peer communication (similar to Facebook), tailored adherence information, and text message dose reminders, and text message adherence, mood, and substance use self-monitoring. An 8-week pilot study showed high feasibility (90%), acceptability, and significant improvement in self-reported ART adherence [48] and the intervention is currently undergoing an RCT in New York City [49]. AllyQuest is an HIV medication adherence and social support app (for Android and iPhone) designed for MSM age 18 to 29. The app components were informed by SCT and the Fogg Behavioral Model (FBM) [50] of persuasive technology. In a four-week pilot study, greater app use was associated with significant increases in knowledge about HIV and confidence in ability to reliably take ART [51]. A third example is the Youth mHealth Adherence Intervention for HIV+ YMSM [52]. This tailored intervention app for Android phone will support ART adherence and engagement in care for MSM age 14 to 24 and includes a customizable avatar, medication reminders and tracking, and social support features (anonymous chat, ability to send “kudos”). Gamification features include a point system, leader board, and ability to unlock new accessories. A feasibility study (n=10) anticipated beginning enrollment in 2017 [52, personal communication May 2, 2017].

Alongside ART adherence, mHealth interventions can be used to support sexual risk reduction among HIV-positive MSM. This is a critical need for curtailing the epidemic among MSM given suboptimal adherence and viral suppression in the context of high rates of condomless anal sex [53*]. Two recent mHealth interventions explicitly designed for HIV-positive MSM focus on sexual risk reduction [54**, 55*]. One study reported on Sex Positive! an intervention comprised of 10 video vignettes (optimized for mobile viewing) that utilize SCT and social learning theory to increase critical thinking about HIV transmission and status disclosure [54**].

Challenges to developing, delivering and evaluating mHealth adherence interventions

Several gaps and challenges offer opportunities for significant advances to the field of mHealth interventions for ART adherence. First, there is interest and acceptability to use mHealth technologies to coordinate care between patients and providers (e.g. dashboards) [42**, 56*]. Dashboards can provide an easily interpretable, real-time overview of a patient’s ART tracking and other health indicators or behaviors (e.g. side-effects, alcohol consumption). This information can be used to provide tailored feedback to patients both at and between in-office appointments. Barriers to dashboard use include physician concerns about the privacy of patient information, ease of access/use, lack of coordination between dashboards and electronic medical records, and time restrictions both during and between patient visits [56*].

Second, as with most adherence interventions, the accurate measurement of adherence barriers and adherence, and connection to clinical outcomes remains a challenge. The development of mHealth interventions typically follows the pattern of formative work to identify barriers to adherence and desired mHealth intervention features, followed by usability or pilot testing, and eventually an RCT. Yet, common self-report adherence barriers (e.g. “I forgot”) that arise in formative work may not correlate with clinical outcomes [57]. Furthermore, memory devices and reminders alone are likely to be insufficient for overcoming the significant individual and structural-level barriers to adherence that many MSM face [58*]. These considerations should affect the way formative work and intervention design are conducted. Innovative intervention development strategies (e.g. community-engaged research, crowdsourcing [36**, 59*, 60*, 61]) may offer new venues in this regard. Furthermore, while mHealth may facilitate more frequent recording of adherence, at least one study to date found discordance between app-measured adherence and self-report and pharmacy refill, with app-measured adherence being lower [62]. This will be the case if participants do not use the app every day, emphasizing the importance of creating highly engaging apps, considering whether users should be able to back-fill app-based adherence data, including biological outcome measures (viral load), and identifying parameter estimates for adjusting app-reported data. At least two studies in the field are currently gathering these metrics [25**, 49].

Third, as mHealth interventions become more complex, individually-tailored, and multi-feature, the complexity of measuring meaningful or standardized intervention exposure/dose also becomes more complicated. Extremely limited work has been done in this area for HIV interventions (Bauermeister et al., current issue), hampering the ability to identify which intervention components and features are associated with desired outcomes.

Relatedly, the chronicity of HIV raises questions about the use of mHealth to maintain longer-term ART adherence beyond a typical 3 to 12 month intervention period. Extended utility would require resources and innovation to create content and features that are continually new, relevant, and aligned with the evolving evidence base. Further challenges stem from the need to keep up with software and hardware upgrades. The use of open-source software and existing platforms that also evolve over time and the adaptation of existing platforms for new populations can mitigate some of these resource demands. Effective, open-source interventions could also be embedded into commercial platforms (e.g. Apple Health) to maximize uptake. On the side of scientific rigor, there are unanswered questions about whether people actually need to use mHealth tools for long periods of time – or whether the tools can establish self-sustaining skills and patterned behaviors. Furthermore, in trials, participants are asked to use (or be exposed to) mHealth interventions continuously over a set amount of time. However, in real world settings, some of these interventions may be better employed in an “as needed” fashion. Implementation studies and dynamic intervention designs (e.g. Sequential Multiple Assignment Randomized Trials) may offer insight by providing data about long-term mHealth use and effectiveness and testing combinations of mHealth intervention approaches.

Perhaps the greatest area for growth in mHealth interventions for MSM is the exchange of evidence-based mHealth interventions or intervention components across settings and populations. This includes the tailoring and testing of effective general population mHealth interventions for use with MSM, as well as the cultural adaptation and translation to other languages of successful MSM-focused apps, text message-based interventions, and social media approaches.

Conclusion

Several recent mHealth interventions developed specifically for MSM show promise for supporting ART adherence and viral suppression. However, none of the reviewed interventions for MSM measured the impact of an mHealth intervention on viral suppression compared to a control condition. Several studies are planned or underway that will assess multiple features within complex smartphone or internet-based platforms providing the opportunity to advance the evidence base for mHealth supported ART adherence as well as expand the science in mHealth measurement and engagement challenges. Combination interventions that use multiple delivery modalities are a future important area for growth alongside adapting efficacious interventions for new languages and geographic settings. Global saturation of basic phones – and increasingly smartphones – has laid the groundwork for widely scalable mHealth interventions to support ART adherence to achieve viral suppression among significantly more HIV-positive MSM.

Key points.

• Recent mHealth intervention tools to support HIV medication adherence among MSM show acceptability, feasibility, and preliminary efficacy at increasing ART use intentions, self-reported adherence, and viral suppression.

• Additional research is needed in the form of rigorous large-scale trials, evaluation of commercially available medication adherence apps, and development of new methods to accurately measure adherence and assess which clinically-relevant barriers can be addressed using technology-based tools.

• Further development needs for technology-based adherence interventions include end-user engagement features, tools for coordinating patient and provider adherence data (e.g. dashboards), and adaptation of efficacious interventions for new languages and geographic settings.