Table 1.

Recent eHealth/mHealth HIV treatment adherence intervention studies among young people

	Study Population	Description of Study	Key Findings
Formative/Qualitative
Anand [38]	HIV+ Young men who have sex with men (YMSM) and young transgender women (YTW) (14–24 years) on ART recruited from multiple sites in Bangkok, Thailand, n=18	Interviewed 18 behaviorally HIV-infected YMSM/YTW regarding care challenges, identified how eHealth could address care needs, and elicited preferences for eHealth interventions. Preferences for eHealth interventions: a) credible HIV resources; b) forums-connection to others; c) connection to medical experts; d) reminders (with preference for participants choosing the content/timing/frequency); e) inclusion of gamification (e.g., rewards for activities and incentive structure) to increase engagement. Participants also requested video testimonials of YLWH and expert advice videos. Privacy concerns mentioned.	Mean age: 22.5 years Preferences for interventions similar to others Supportive Networks: 72.2% of participants wanted to connect with other YLWH in an online forum Privacy concerns mentioned (e.g., 100% preferred using pseudonym in forum)
Holloway [39]	Black YMSM (18–29 years) recruited from community- based agencies serving Black YMSM in Los Angeles, California; n=41 (46% HIV+)	Six focus groups to evaluate preferences for mHealth prevention and treatment Recommendations: a) holistic health interventions; b) discrete connection to health educators and treatment providers; c) contests and prizes for health games Participants also requested the ability to rate and review local clinics and providers Privacy/confidentiality was paramount to participants	Mean age: 26 years Preferences for interventions similar to others Supportive Networks: participants were torn about whether they should be able to communicate with other users. Many liked the idea of incorporating social media into app to build social support networks with others Privacy concerns were noted (e.g., expressing hesitance about downloading app that might indicate their HIV status to others)
LeGrand [41]	HIV+ YMSM (20–28 years) in North Carolina; n=27 (Phase 2, n=20; Phase 3, n=7)	Focus groups: Three focus groups to (1) assess ART adherence information, motivation, and behavioral skills needs and determine strategies to address these needs via a mobile app, and to gather feedback on the evolving features of an adherence app prototype (Epic Allies) as well as future feature concepts. Suggestions: a) discrete medication reminders (e.g., including option to turn-off); b) connection with others dealing with similar adherence challenges; c) make interactive with games/rewards within app; d) customizable. Usability testing: Usability testing to assess whether users: could successfully navigate features and functions of the app, could comprehend the educational content, and found the app to be engaging and relevant.	Mean age (focus groups): 24 years Mean age (usability testing): 23 years Preferences for interventions similar to others Supportive Networks: In Phase 2, participants requested an app that could be used to connect with other dealing with adherence challenges, while also emphasizing need to maintain anonymity Engagement: gamification End-user involvement: iterative app development incorporating ongoing user feedback in both Phases (e.g., updated clickable prototypes created prior to each focus group based on previous findings)
Outlaw [73]	YLWH (18–24 year) newly recommended to start ART, recruited from 2 sites of NIH Adolescent Medicine Network for HIV/AIDS Interventions (ATN) sites in US; n=10	Initial feasibility of an individually tailored computer- based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Each session was approximately 1 hour, with the 2nd session occurring 1 month after the first. Participants completed a semi-structured face-to-face interview with site staff after each intervention session to provide feedback. Preferences for changes to intervention were largely technical and programmatic (e.g., changing voices of narrative characters, removing character verbalizations (sighs), and adding female characters).	Mean age: 20 years Acceptability: Retention was 100% for both intervention sessions; participants were satisfied with the sessions overall (80% very/mostly satisfied with Session 1; 89% with Session 2) and were satisfied with the amount of assistance they received for managing their adherence to HIV medications (90% satisfied with Session 1 and 89% with Session 2) End-user involvement: Intervention development occurred in collaboration with three youth advisory groups.
Rana [35]	YLWH (14–24 years) on ART in two clinics in Kampala, Uganda; n=39 (51.3% male)	Six focus groups conducted as part of formative work for developing an SMS-based intervention called Reminding Adolescents to Adhere (RATA) 2 of 6 focus groups were with minors (<18 years old) Challenges to the intervention (reported by youth): a) not all youth have access to mobile phones; b) sharing phones would be problematic for youth who have not disclosed their status to those with whom they share phones; c) some youth reported facing restrictions on their phone use (particularly younger as well as female participants); d) concerns about accidental disclosure of HIV status No consensus for frequency of messages Preferences: a) reminders sent around time of medication dosing; 2) two- way SMS for support	Mean age: 19.5 years Availability: 90% knew how to write, read and send texts, 72% owned a cell phone Acceptability: Almost all participants (97%) felt that the RATA intervention would help them improve their adherence Preferences for interventions similar to others Privacy concerns mentioned (e.g., noted that 41% of all participants reported sharing a phone with others)
Saberi (2013) [44]	Black YLWH (18–29 years old) on ART (>30 days) recruited from HIV clinics in San Francisco, California; n=14 (86% male)	Pilot Study with no comparison condition Assessed the feasibility and acceptability of a telehealth (remote videoconferencing) ART counseling intervention provided by a HIV clinical pharmacist. Participants received one private telehealth counseling session (~45 minutes long) followed by a semi-structured qualitative interview to explore likes/dislikes of the format, modality, and content; potential impact on adherence; privacy issues; and interaction quality. Participants described telehealth as convenient and ef cient, with positive impact on their knowledge and less intimidating than in-person visits.	Mean age: 24 years Privacy: Perceived telehealth as private (participants were in private room at UCSF, not at home) Design: personal support and counseling via telehealth provided by the HIV clinical pharmacist
Saberi (2016) [40]	HIV+ youth (18–29 years) recruited from clinics serving individuals living with HIV in the San Francisco Bay Area; n=17 (88.2% male)	Four focus groups to better understand preferences for mobile apps in general and to inform the design of a mHealth app aimed at improving retention and engagement in HIV care and adherence to ART. Suggestions: a) ability to connect to a community of other YLWH; b) access to healthcare providers; c) ability to track personal data and information (such as laboratory data); d) provision of health news and education. Privacy was a key factor for all participants (e.g., participant suggested passcodes, use of pseudonyms and avatars)	Mean age: 25 years Preferences for interventions similar to others, except that participants did not express an interest in having a game component in the mobile phone app. Supportive Networks: Participants wanted peer support from other YLWH (e.g., recommendations for a closed group invited by healthcare provider to have a “true community of YLWH”) Privacy concerns mentioned
Pilot/RCT
Dowshen [33]	YLWH (14–29 years) on ART with adherence problems recruited from large US city; n=25 (92% male)	Analysis from Pilot Study [74] with no comparison condition Study consisted of 24 weeks of personalized daily SMS reminders (ITR-Interactive text response) with follow-up message 1 hour later asking whether participant took their medication. Participants asked to respond with 1 to indicate yes and 2 to indicate no. Personalized messages were crafted by the participant.	Mean age: 23 years Engagement: responded to prompts 61.4% of the time Effectiveness/Sustained response: ITR and VAS measures moderately correlated during first 6 weeks of study. Results of pilot showed almost 20% improvement in self-reported adherence from baseline to week 12 (mean VAS baseline 73.7% and week 12 = 93.3%). This was sustained at week 24 (mean VAS = 93.1%).
Garofalo [32]	Poorly adherent YLWH (66% VS at baseline) (16–29 years) recruited from community- based health centers in Chicago, n=105 (80% male)	Pilot RCT Personalized 2-way text message reminders daily for 6 months with f/u 15 minutes later asking whether participant had taken their medication. Both initial message and f/u messages were designed by the youth. Comparison condition (and intervention) received standard -of-care adherence education at baseline (i.e., 20- minute animated tutorial on importance of adherence)	Mean age: 24 years Engagement: responded to prompts 58% of the time Effectiveness/Sustained response: moderate increase in self-reported adherence at 3 months, not significant at 6-months; The average effect estimate over the 6-month intervention period was significant for 90 % adherence (OR = 2.12, 95 % CI 1.01– 4.45, p < .05) and maintained at 12- months (6 months post-intervention). Acceptability: high satisfaction scores (e.g., 100% would recommend to a friend, 81% wanted to continue getting messages after study conclusion) Privacy noted as concern (e.g., to protect confidentiality, staff encouraged participants to delete messages after taking medication and to use messages that would not reveal status)
Linnemayr [34]	YLWH (15–22 years) at 2 HIV clinics in Kampala, Uganda; n=332 (39% male)	Year-long parallel individual-RCT Assigned in a 1-to-1-to-1 ratio to a weekly SMS message group, weekly SMS message with response option group, or a usual-care control group. Messages in both SMS groups were sent at 9AM on Sunday and content was standardized. For the 1-way group, the message was “We hope you are feeling well today.” For the 2-way group, the message was “We hope you are feeling well today. Reply 1 if well, 2 if unwell.” Respondents in 2-way group who did not respond within 48 hours received a f/u message “How are you? We have not heard back from you. Reply 1 if well, 2 if unwell.” No additional messages or follow-up calls were provided after this to the non-responders. Those who said “unwell” received call from study coordinator within 24 hours.	Mean age: 18 years Engagement: 86.4% of messages were successfully sent/marked as “delivered” to the participant’s phone. Among those in 2-way group, response rate was 28.4% Effectiveness/Sustained response: electronically measured mean adherence was 67% in controls, 64% in 1-way texting group and 61% in 2-way group
Menza [75]	HIV+ Black YMSM (18 - 30 years) in North Carolina, n=199	Observational analysis of RCT [76, 77] Participants in healthMpowerment (intervention 3 months with follow-up to 12 months), a RCT of an Internet-based HIV prevention intervention vs. information control website, to identify time-varying correlates of self-reported viral suppression using relative risk (RR) regression.	Median age: 24.5 years Feasibility/Acceptability: Retention at the 12-month visit was 84%. Engagement: Moderate usage of intervention with large range from very low/no users to high/super users. Participants used their assigned Web site for a median of 11 minutes (IQR, 5–38.5 minutes; range, 1–1250 minutes) and a mean (SD) of 73 (190) minutes. Effectiveness: Increase in VS seen over time but no difference between intervention/control groups One hundred five (65%) of 162 participants reported being undetectable at baseline. At 3, 6, and 12 months, 83 (72%) of 115, 84 (82%) of 103, and 101 (86%) of 117 reported an undetectable VL, respectively.
Naar-King [43]	YLWH (16–24 years) newly prescribed ART (<12 weeks ago) recruited from 8 sites of NIH ATN sites in US; n=76 (80.3% male)	Pilot RCT Two session computer-delivered motivational intervention to facilitate adherence (MESA: Motivational Enhancement System for Adherence). 2nd session occurred one month after first session. Sessions took 30 minutes to complete. Comparison was an active 2 session computer-delivered nutrition and physical activity control.	Mean age: 20.3 years Feasibility/Acceptability: high satisfaction ratings; high retention at 3 and 6 months (92% both) Effectiveness: Effect sizes suggested that the intervention group showed a greater drop than controls in VL from baseline to 6 months, and had greater percent undetectable by 6 months.
Stankievich [78]	YLWH (6–25 years) on ART, VL >1000 copies/mL recruited from tertiary hospital in Buenos Aires, Argentina; n=22 (32% male)	Pilot Study with no comparison condition Intervention based on a mobile generic contact made twice a month by a health worker using the participant’s preferred mode of contact (e.g., WhatsApp, text messages, and Facebook) for 32 weeks The messages included short questions about the status of the patient and medication-related issues. The content of messages was identical across the intervention group. If the patient or parent required additional information, a feedback phone call or contact message could be generated (i.e., “extended communication”)	Mean age: 17.2 (range 6–25); 11 participants were minors (<18). NB: 7/11 minor participants were contacted through parents. Engagement: Each participant received a total of 16 contacts, 84% (296) were answered by the patient. 54%(189) of the contacts generated extended communications Effectiveness: After the strategy implementation VLs from 20/22 participants were available. 13/20 (65%) were undetectable
Protocols currently being developed/tested
Inwani [58]	Adolescent girls and young women (AGYW) in the age range of 15 to 24 years in Homa Bay County, western Kenya, anticipating n=108	Newly diagnosed AGYW with HIV will be enrolled in the SMART trial pilot to determine the most effective way to support initial linkage to care after a positive diagnosis. Participants will be randomized to standard referral (counseling and a referral note) or standard referral plus a single SMS text message; those not linked to care within 2 weeks will be re-randomized to receive an additional SMS text message or a one-time financial incentive. Study will also examine the incremental cost per HIV- positive female linked to care.	Design: SMART trial nested within larger implementation science study (also examining effective recruitment/HIV testing strategies to identify HIV+ AGYW). SMS: Part of package. After successful linkage to care, participants will receive motivation SMS for adherence to medication and care Incentives: Participants in SMART trial will be given a study phone to ensure lack of access is not barrier to enrollment)
Mavhu [36]	HIV-positive adolescents (13– 19 years) and eligible for ART in 2 districts in Zimbabwe, expected n=500	Sixteen clinics were randomized to either enhanced ART-adherence support or standard of care. Both arms receive ART and adherence support provided by adult counselors and nursing staff. Adolescents in the intervention arm additionally attend a monthly support group, have a designated Community Adolescent Treatment Supporter (CATS), and receive follow-up through personalized SMS and calls plus home visits from the CATS. Type and frequency of contact is determined by whether the adolescent is "stable" or in need of enhanced support. Stable adolescents receive a monthly home visit plus a weekly, individualized SMS. An additional home visit is conducted if participants miss a scheduled clinic appointment or support-group meeting. Participants in need of enhanced support receive bi-weekly home visits, weekly phone calls and daily SMS.	SMS: Part of package of community- based interventions. SMS messages written and sent by CATS Design: In-person + technology
Tanner [37]	Racially and ethnically diverse MSM (13–34 years), living with HIV`	Describes the foundation and development of weCare, a tailored social media intervention designed to improve health outcomes among a diverse group of young MSM living with HIV. The weCare Health Educator (a young, Latino MSM) will use established social media platforms (e.g., Facebook, text, apps) to send theory-based messages to participants based on the participant’s preference for mode of connection The Health Educator will also manage an optional Facebook secret group for participants and will also have some face-to-face interactions with participants (e.g., at clinic when participants come for appointments)	Supportive networks: utilization of existing social media platforms; Health Educator provision of support and personalized guidance End-user involvement: intervention development guided by a steering committee comprised of members from the local catchment area, including racially and ethnically diverse YMSM (some of whom are HIV positive) and the project team Design: Messages sent from Health Educator, secret group, face-to-face- sessions