PONE-D-21-39720Barriers to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review protocolPLOS ONE

Dear Dr. Nyasulu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Professor Kwasi Torpey, MD PhD MPH

Academic Editor

PLOS ONE

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4. We note that you have referenced (ie. Bewick et al. [5]) which has currently not yet been accepted for publication. Please remove this from your References and amend this to state in the body of your manuscript: (ie “Bewick et al. [Unpublished]”) as detailed online in our guide for authors

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

This study is extremely important as it seeks to highlight our understanding of adherence among adolescents. The manuscript is nicely written and very easy to follow. In East and south Africa region 90% of PLHIV know their status 78% are on ART and 72% are virally suppressed. for West Africa it is 81%-77%-62%. Whilst the authors have given some data, highlighting the proportions among adolescents compared to adults makes a compelling case. In addition, the authors should correct minor typo in the methods section (pinion piece - opinion piece)

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript presents the protocol of a systematic review for barriers of adherence to ARVs among HIV positive adolescents in SSA. Adherence to ARVs has been reported to be lower in adolescents and this has has also been reflected in their negative treatment outcomes. This study hence seeks to understand the barriers of adherence to ARVs among adolescents in a systematic review study. The authors have chosen to review studies from 2010 when WHO reviewed its treatment guidelines.

The manuscript is well written and structured. The authors have identified the problem and the research gap. It is also novel as it is a mixed method systematic review. The methods for the review for both quantitative and qualitative studies have been well explained in the methods section.

The manuscript does not have any major weakness. However, in terms of relevance, the authors indicate that the study will be the first to track barriers of ART but it is not clear how this information will be useful in changing the negative HIV treatment outcomes in adolescents. It is not clear what new knowledge this study adds to existing studies that have reported barriers of adherence to ARVs among adolescents. I recommend that the authors could consider the use of the mixed method approach to show the added value this study will have to previous research.

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Reviewer #1: No

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PONE-D-21-39720R1Barriers to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review protocolPLOS ONE

Dear Dr. Nyasulu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

 At this stage the staff editors from PLOS ONE have some minor concerns regarding your submission which must be addressed for this submission to meet PLOS ONE's publication criteria. These are appended below in the section titled 'Journal Requirements'. Could you please carefully revise the manuscript to respond to the concerns raised?

Please submit your revised manuscript by Jul 16 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the staff editors. You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Sebastian Shepherd

Staff Editor

PLOS ONE

Journal Requirements:

1) In your manuscript you indicate you will include publications from 2010 - 2021. Could you please 

A) Outline why studies published before 2010 will not be included

and

B) Update your manuscript to indicate that you will include studies published in 2022 (to keep the submissions included up to date)

2) In lines 294-296 the rationale for this systematic review is given with the following text: "In our knowledge, this review will be the first study to track the barriers to ART adherence among ALHIV aged 10 to 19 years in Sub-Saharan Africa after the WHO recommendations post 2006."

However we have identified the following systematic reviews which discuss barriers to ART adherence:  

• Shubber, Z., Mills, E.J., Nachega, J.B., Vreeman, R., Freitas, M., Bock, P., Nsanzimana, S., Penazzato, M., Appolo, T., Doherty, M. and Ford, N., 2016. Patient-reported barriers to adherence to antiretroviral therapy: a systematic review and meta-analysis. PLoS medicine, 13(11), p.e1002183. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002183
• Kim, S.H., Gerver, S.M., Fidler, S. and Ward, H., 2014. Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis. AIDS (London, England), 28(13), p.1945 https://journals.lww.com/aidsonline/fulltext/2014/08240/adherence_to_antiretroviral_therapy_in_adolescents.12.aspx
• Ammon, N., Mason, S. and Corkery, J.M., 2018. Factors impacting antiretroviral therapy adherence among human immunodeficiency virus–positive adolescents in Sub-Saharan Africa: a systematic review. Public health, 157, pp.20-31. https://www.sciencedirect.com/science/article/abs/pii/S0033350617304237?via%3Dihub

We are aware that these may differ slightly in population, and that the most recent of these reviews is from 4+ years ago, however, can you please cite these systematic reviews and outline how your work will advance on these works. 

3) Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have shown the relevance of the study and how the findings will be useful in changing the negative treatment outcomes among adolscents

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Barriers to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review protocol

PONE-D-21-39720R2

Dear Dr. Nyasulu,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

George Vousden

Staff Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: