Dear Dr. Lawrence,

Thank you very much for submitting your manuscript "The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: findings from a qualitative methods study of participants and researchers in Botswana and Uganda" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by two independent reviewers with relevant expertise. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Chaoyang Xue, Ph.D.

Academic Editor

PLOS Neglected Tropical Diseases

Elsio Wunder Jr

Section Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: (1) consider including the interview questions into supplemental materials (were the same interview questions used in all study sites?)

(2) Please describe steps taken to ensure that the interviewer was not inadvertently influencing the participant’s opinion in favor of one arm versus the other.

Reviewer #2: The method is in order

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: (3) If possible, consider showing the participants’ demographic information at each study site, including the language. These data can be organized in a table or graph format

(4) Instead of using subjective terms like “general preference”, “most participants”, “clear preference”, etc., please consider including the actual numbers of participants favoring one arm of the trial over the other… Is it possible to assign numbers to these terms?

Reviewer #2: The results are in order

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: (No Response)

Reviewer #2: The conclusiond drawn form the study based on the set out objectives were in order.

The research limitations were also discussed.

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: (No Response)

Reviewer #2: The conclusion from the paper is in line with known knowledge evidenced by the WHO 2022 guideline and the paper (ref 21) the authors cited.

The extra information the authors provided was evidence for acceptability of Ambisome regimen I am not sure if this is enough data for a full research article.

The sample size is very small

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: The manuscript by Lawrence et al describes results of a qualitative follow up study to the Ambisome Therapy Induction Optimization clinical trail aimed at investigating the acceptance of the treatment regiments by patients, their caregivers and healthcare workers participating in the clinical trial. The study is based on the interviews and direct observations. The manuscript is well written, the results are important. In my opinion, the paper will benefit from providing more concrete data in support the observed tendencies. A few suggestions are below:

(1) consider including the interview questions into supplemental materials (were the same interview questions used in all study sites?)

(2) Please describe steps taken to ensure that the interviewer was not inadvertently influencing the participant’s opinion in favor of one arm versus the other.

(3) If possible, consider showing the participants’ demographic information at each study site, including the language, in which the interview was conducted. These data can be organized in a table or graph format

(4) Instead of using subjective terms like “general preference”, “most participants”, “clear preference”, etc., please consider including the actual numbers of participants favoring one arm of the trial over the other… Is it possible to assign numbers to these terms?

Reviewer #2: The paper is good and well-written.

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Reviewer #1: No

Reviewer #2: No

Figure 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. 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 us at figures@plos.org.

Data Requirements:

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Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References

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.

Dear Dr. Lawrence,

We are pleased to inform you that your manuscript 'The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: findings from a qualitative methods study of participants and researchers in Botswana and Uganda' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Chaoyang Xue, Ph.D.

Academic Editor

PLOS Neglected Tropical Diseases

Elsio Wunder Jr

Section Editor

PLOS Neglected Tropical Diseases

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