Effect of a WeChat-Based Intervention (Run4Love) on Depressive Symptoms Among People Living With HIV in China: Randomized Controlled Trial

Background People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population. Objective The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China. Methods We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants’ hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants’ progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument. Results Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=−5.77, 95% CI −7.82 to −3.71; P<.001; standard effect size d=0.66). The mean changes in CES-D score from baseline to the 6- and 9-month follow-ups between the two groups remained statistically significant. No adverse events were reported. Conclusions The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention. Trial Registration Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF)

Is this a full powered effectiveness trial or a pilot/feasibility trial? * Manuscript tracking number * If this is a JMIR submission, please provide the manuscript tracking number under "other" (The ms tracking number can be found in the submission acknowledgement email, or when you login as author in JMIR. If the paper is already published in JMIR, then the ms tracking number is the fourdigit number at the end of the DOI, to be found at the bottom of each published article in JMIR) You're editing your response. Sharing this URL allows others to also edit your response.
FILL OUT A NEW RESPONSE 1a-i) Identify the mode of delivery in the title Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if o ine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.
Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. The title indicates that the intervention was WeChat-based.
You're editing your response. Sharing this URL allows others to also edit your response. Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support").
Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. The intervention "Run4Love" contains multiple components and has been elaborated in details in the manuscript.
1a-iii) Primary condition or target group in the title Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial Does your paper address subitem 1a-iii? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we state that the target group is people living HIV.
You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that Run4Love intervention was built up adapted cognitive behavioral stress management courses and included weekly reminders, and tailored feedback.
1b-ii) Level of human involvement in the METHODS section of the ABSTRACT Clarify the level of human involvement in the abstract, e.g., use phrases like "fully automated" vs. "therapist/nurse/care provider/physician-assisted" (mention number and expertise of providers involved, if any). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 1b-iii?

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Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that participants were recruited (face-to-face) in an outpatient clinic. The assessments (baseline and follow-up surveys) was administered using a tablet. The trial was not blind to the participant or investigators.
You're editing your response. Sharing this URL allows others to also edit your response. 1b-iv) RESULTS section in abstract must contain use data Report number of participants enrolled/assessed in each group, the use/uptake of the intervention (e.g., attrition/adherence metrics, use over time, number of logins etc.), in addition to primary/secondary outcomes. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) Does your paper address subitem 1b-iv?

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Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that we recruited a total of 300 participants and they were randomly assigned to intervention or control with a ratio of 1:1.
1b-v) CONCLUSIONS/DISCUSSION in abstract for negative trials Conclusions/Discussions in abstract for negative trials: Discuss the primary outcome -if the trial is negative (primary outcome not changed), and the intervention was not used, discuss whether negative results are attributable to lack of uptake and discuss reasons. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) Does your paper address subitem 1b-v?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. The Run4Love was a successful trial. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that despite a growing interest on mHealth interventions among people living with HIV (PLWH), especially on its initial e cacy on improving medication adherence, few mHealth interventions exist to improve mental health outcomes of PLWH. Data are further scarce from such studies based on a randomized controlled trial.
Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we hypothesized that the intervention group would have greater improvement in the measures of depressive symptoms, quality of life, and other psychosocial outcomes, compared to the control group in usual care.
Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that "The study was a parallel-design RCT. It was conducted in Guangzhou, China between September 2017, and October 2018. Participants You're editing your response. Sharing this URL allows others to also edit your response. 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons subitem not at all important 1 2 3 4 5 essential 4a) Eligibility criteria for participants g p p were randomized 1: 1 to 2 groups: a WeChat-based mHealth intervention group or a usual care waitlist control group." Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. We did not make any change to the methods after trial commencement.

3b-i) Bug xes, Downtimes, Content Changes
Bug xes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug xes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have in uenced study design such as staff changes, system failures/downtimes, etc.
[2]. Does your paper address subitem 3b-i? Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A.
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FILL OUT A NEW RESPONSE Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that "The inclusion criteria of the participants were: 1) 18 years or older; 2) HIV seropositive; 3) having elevated depressive symptoms (measured by the Center for Epidemiological Studies Depression Scale, CES-D ≥ 16); 4) willing to provide hair samples, and 5) using WeChat. The criteria for exclusion were: 1) currently on psychiatric treatment; 2) unable to nish the screening or baseline survey; 3) unable to read or listen to the materials sent via WeChat (i.e., short articles, audios, posters), or 4) unable to engage in physical activities due to medical reasons."

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clari ed.
Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, our participation eligibility include smart phone ownership and using WeChat.
4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. o ine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email con rmation, phone calls) were used to detect/prevent these.
You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. In the Methods, we stated that participants were recruited from an outpatient clinic (face-to-face); they completed the baseline survey on a tablet at the time of recruitment. The intervention assignment was not blind, participants needed to give research staff their WeChat ID and phone number.

4a-iii) Information giving during recruitment
Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results.
Does your paper address subitem 4a-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that "Patients in the waiting area were invited by the research staff to participate in the study. They rst completed a brief screening questionnaire in a private space. Those who met the eligibility criteria (see below) were provided with a pamphlet with description of the Run4Love study and invited to join the study. Patients interested to participate were given further information about the study." Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" You're editing your response. Sharing this URL allows others to also edit your response. 5) The interventions for each group with su cient details to allow replication, including how and when they were actually administered Copy and paste relevant sections from the manuscript (include quotes in quotation marks like this to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that the study location was a large hospital in Guangzhou China.

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4b-i) Report if outcomes were (self-)assessed through online questionnaires Clearly report if outcomes were (self-)assessed through online questionnaires (as common in webbased trials) or otherwise.
Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that the assessments were conducted on a tablet.

4b-ii) Report how institutional a liations are displayed
Report how institutional a liations are displayed to potential participants [on ehealth media], as a liations with prestigious hospitals or universities may affect volunteer rates, use, and reactions with regards to an intervention.(Not a required item -describe only if this may bias results) Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

Your answer
You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 5-i?

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Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. The program was developed by our research team.

5-ii) Describe the history/development process
Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results.
Does your paper address subitem 5-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

Your answer
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5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial. Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).
Does your paper address subitem 5-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

Your answer
You're editing your response. Sharing this URL allows others to also edit your response. -v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing owcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing owcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scienti c reporting.

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Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.
Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

Your answer
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5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speci c group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).
Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we stated that participants will receive information on their own WeChat account on their own smartphones. The study does not require downloading a new app or logging in. Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we described the Run4Love intervention components, functions, and theoretical framework, and comparator on manuscript (p7-8). The intervention protocol was also detailed in a published paper, reference #15.

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.
Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21generalizability).
You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer 5-xi) Report any prompts/reminders used Report any prompts/reminders used: Clarify if there were prompts (letters, emails, phone calls, SMS) to use the application, what triggered them, frequency etc. It may be necessary to distinguish between the level of prompts/reminders required for the trial, and the level of prompts/reminders for a routine application outside of a RCT setting (discuss under item 21 -generalizability).

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Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we reported that participants received weekly reminders on WeChat for physical activity and personalized feedback.

5-xii) Describe any co-interventions (incl. training/support)
Describe any co-interventions (incl. training/support): Clearly state any interventions that are provided in addition to the targeted eHealth intervention, as ehealth intervention may not be designed as stand-alone intervention. This includes training sessions and support [1]. It may be necessary to distinguish between the level of training required for the trial, and the level of training for a routine application outside of a RCT setting (discuss under item 21 -generalizability.
Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks like this to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. We did not have any co-intervention.

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Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We detailed primary outcome measure and secondary outcome measures, including how they were assessed.
6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed If outcomes were obtained through online questionnaires, describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed [9].
Does your paper address subitem 6a-i?

Copy and paste relevant sections from manuscript text
Your answer 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was de ned/measured/monitored Describe whether and how "use" (including intensity of use/dosage) was de ned/measured/monitored (logins, log le analysis, etc.). Use/adoption metrics are important process outcomes that should be reported in any ehealth trial.
You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address CONSORT subitem 6b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. The trial protocol was pre-registered in www.chictr.org.cn, we did not change any trial outcome after the trial commenced.

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You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 7a-i?

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Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not in this manuscript, but sample size calculation was reported in another paper on study protocol, which as published last year.
Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A.
Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript) or elaborate on this item by providing additional You're editing your response. Sharing this URL allows others to also edit your response. 8b) Type of randomisation; details of any restriction (such as blocking and block size) 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A.

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Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that "Allocation to treatment group was carried out by a computer-generated randomization list with a block size of 4 using SAS software version 9.4 (SAS Institute, Inc., Cary, NC, USA). By the nature of the trial design, neither research staff nor participants were blinded to the intervention." Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. See responses to 8b.
Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional You're editing your response. Sharing this URL allows others to also edit your response. 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering co-interventions (if any).

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Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. see responses to 8b.
11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectations -discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".
Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript) or elaborate on this item by providing additional You're editing your response. Sharing this URL allows others to also edit your response. 11b) If relevant, description of the similarity of interventions (this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that the intervention assignment was not blind to the participants or research staff.

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Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A.
Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We reported details of statistical analyses. We stated that "For the primary outcome, group differences in CES-D scores over the 9 months of the trial were estimated using a linear mixed-effects model (LMM) with repeated measures, adjusting for baseline CES-D score, time, and other baseline characteristics [32].
In addition, interactions between group and time were also examined in LMM. R package 'nlme' (R Foundation, version 3.4.2) was used to conduct the LMM analysis. Similar analyses were repeated for secondary outcomes. " You're editing your response. Sharing this URL allows others to also edit your response. subitem not at all important 1 2 3 4 5 essential 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses 12a-i) Imputation techniques to deal with attrition / missing values Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).

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Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that "Analyses for changes in outcomes between baseline and each follow-up were performed using multiple imputations for the missing data [31]. The R package 'mice' (R Foundation, version 3.4.2) was used to obtain 80 imputed data sets. Variables used for imputation included age, gender, marital status, sexual orientation, education, body mass index (BMI), family monthly income, household registration, duration of HIV infection, and outcome values. " Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. We did not report subgroup analysis, as the intervention and control group were comparable at baseline.
You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we reported that the study protocol was approved by the Institutional Review Board of Sun Yat-sen University.

x26-ii) Outline informed consent procedures
Outline informed consent procedures e.g., if consent was obtained o ine or online (how? Checkbox, etc.?), and what information was provided (see 4a-ii). See [6] for some items to be included in informed consent documents.
Does your paper address subitem X26-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline) You're editing your response. Sharing this URL allows others to also edit your response.

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center 13b) For each group, losses and exclusions after randomisation, together with reasons Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we reported that a total of 300 participants were enrolled in the study. The follow-up rates were 91.3% (92.7% in intervention and 90.0% in control), 88.3% (88.0% in intervention and 88.7% in control), and 86.7% (88.7% in intervention and 84.7% in control) at 3, 6 and 9 months respectively.
Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT ow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study You're editing your response. Sharing this URL allows others to also edit your response. Yes. We reported attrition rate at each follow-up, also see response to 13a.

13b-i) Attrition diagram
Strongly recommended: An attrition diagram (e.g., proportion of participants still logging in or using the intervention/comparator in each group plotted over time, similar to a survival curve) or other gures or tables demonstrating usage/dose/engagement.

Does your paper address subitem 13b-i?
Copy and paste relevant sections from the manuscript or cite the gure number if applicable (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer Does your paper address CONSORT subitem 14a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we speci ed the recruitment and follow-up with a diagram (Figure 1).
14a-i) Indicate if critical "secular events" fell into the study period Indicate if critical "secular events" fell into the study period, e.g., signi cant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 14a-i?

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Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. The trial was not ended early. It followed the pre-registered protocol.
Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. Table 1 lists detailed baseline demographic and clinical characteristics of each group.

15-i) Report demographics associated with digital divide issues
In ehealth trials it is particularly important to report demographics associated with digital divide issues, such as age, education, gender, social-economic status, computer/Internet/ehealth literacy of the participants, if known.
You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

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No. Our participation eligibility include Owning a smartphone and using WeChat, so we did not report demographics associated with digital divide issues.
16-i) Report multiple "denominators" and provide de nitions Report multiple "denominators" and provide de nitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speci c pre-de ned time points of interest (in absolute and relative numbers per group). Always clearly de ne "use" of the intervention.
Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We reported the analysis followed the original assigned groups.

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).
You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we reported that the primary analysis used intent-to-treat analysis.

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Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, for all primary and secondary outcomes, we reported effect sizes and 95% con dence intervals ( Table 2, Table 3).

17a-i) Presentation of process outcomes such as metrics of use and intensity of use
In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational de nitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is de ned (e.g., timeout after idle time) [1] (report under item 6a).
Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study You're editing your response. Sharing this URL allows others to also edit your response. Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. All outcomes were continuous.

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Does your paper address CONSORT subitem 18? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study N.A. We didn't perform any subgroup analyses as it was not in the pre-registered trial protocol.

18-i) Subgroup analysis of comparing only users
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).
Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use)

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Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use).
You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We stated that "The WeChat-based mHealth intervention Run4Love signi cantly reduced depression severity CES-D by 5.77 points at 3 months compared with usual care; and the improvement sustained at 6-and 9-month follow-ups with a medium to large effect size of .66 at 3 months." "The intervention also improved QOL, self-e cacy, SWCQ positive coping, reduced perceived stress, and depression severity PHQ-9, compared to the control group at 3 months. The improvements of such secondary outcomes as QOL and SWCQ positive coping remained signi cant at 6-and/or 9-month follow-ups. ".

22-ii) Highlight unanswered new questions, suggest future research
Highlight unanswered new questions, suggest future research.
Does your paper address subitem 22-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We also note that older participants were also more likely to drop out of the study despite the high retention rate, suggesting a possible digital divide. Our subgroup analyses showed that younger and unmarried participants bene ted more from the intervention that their counterparts. It requires further research on effective strategies to deliver mental health services to older people living with HIV and depression.
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20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events.
Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes. We listed 5 major limitations in Discussion. For example, "Fourth, the research staff were not blind to group allocation; but the use of an electronic questionnaire on a tablet may limit the bias introduced by assessors."

21-i) Generalizability to other populations
Generalizability to other populations: In particular, discuss generalizability to a general Internet population, outside of a RCT setting, and general patient population, including applicability of the study results for other organizations You're editing your response. Sharing this URL allows others to also edit your response. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes, we acknowledge the limited generalizability of the study. For example, "First, most participants were young MSM recruited from a large hospital in South

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China. The ndings from the study might not be generalizable to other PLWH, especially older PLWH, those living in rural areas, or were not infected through homosexual transmission." 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other co-interventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

Your answer
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