Dear Dr Falcao,

Thank you very much for submitting your manuscript "Paracoccidioidomycosis in people living with HIV/AIDS: a historical retrospective cohort study in a national reference center for infectious diseases, Rio de Janeiro, Brazil" 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 several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

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

[1] A letter containing a detailed list of your responses to the 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.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. 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,

Ahmed Fahal, FRCS, FRCSI, FRCSG, MS, MD, FRCP(London)

Deputy Editor

PLOS Neglected Tropical Diseases

Ahmed Fahal

Deputy 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: Are the objectives of the study clearly articulated with a clear testable hypothesis stated? No

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

Is the population clearly described and appropriate for the hypothesis being tested. Yes

Is the sample size sufficient to ensure adequate power to address the hypothesis being tested? No

Were correct statistical analysis used to support conclusions? No

Are there concerns about ethical or regulatory requirements being met? No

--------------------

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: Does the analysis presented match the analysis plan? Yes

Are the results clearly and completely presented? Yes

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

--------------------

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: Are the conclusions supported by the data presented? No

-Are the limitations of analysis clearly described? No

Do the authors discuss how these data can be helpful to advance our understanding of the topic under study? No

Is public health relevance addressed?Yes

--------------------

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)

--------------------

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: 1-The abstract needs to be improved and must include more data related with the study.

2-The Key words were not described.

3-The Results: They are very extensive, repetitive in both text and tables.

4-The Tables could be condensed in one or two.

5- the presented figures, maybe the number two has more relevance to be included into the paper. the others could be removed.

6-The discussion section is very extensive, few adequated and needs to be more concise and focalized on HIV/ PCM coinfection together with the literature data.

7-Generalizations are used with frequency and they must be avoided, due to the small size of the individuals included.

Minor comments.

1-Please verify reference number 12. It is inadequate for citation. See Almeida et al 2017.Benard et al 2000. Some of the references are few originals

2-The paragraph between lines 87-90 is inadeaquate.

3-There is a contradiction in values related with the prevalence of the acute clinical form of PCM <10% line 281, and 26% line288.

4-It would be interesting to cite the reference whic describe 12% of PCM in HIV infected patients Line 90.

5-It is very importan to clarify why the high variability of therapy time in these patients From 12 to 60 months?This is very different from elsewere

6-I suggest to improve the information and disccussion of the two cases who developed IRIS. This is an exciting matter to give an upgrade in your manuscript.

7-The English style must be reviewed.

--------------------

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.

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Reviewer #1: 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:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

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

Dear Dr Falcao,

We are pleased to inform you that your manuscript 'Paracoccidioidomycosis in people living with HIV/AIDS: a historical retrospective cohort study in a national reference center for infectious diseases, Rio de Janeiro, Brazil' 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,

Ahmed Fahal, FRCS, FRCSI, FRCSG, MS, MD, FRCP(London)

Deputy Editor

PLOS Neglected Tropical Diseases

Ahmed Fahal

Deputy Editor

PLOS Neglected Tropical Diseases

***********************************************************

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

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

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

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?No

o

-Were correct statistical analysis used to support conclusions?Yes

-Are there concerns about ethical or regulatory requirements being met?No

**********

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: Does the analysis presented match the analysis plan? Yes

-Are the results clearly and completely presented?Yes

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

**********

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: -Are the conclusions supported by the data presented?Yes

-Are the limitations of analysis clearly described?Yes

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

-Is public health relevance addressed? Yes

**********

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: None

**********

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 authors present a cases serie report of paracoccidioidomycosis in HIV -infected patients. They describe the most relevant epidemiological , clinical and outcome features of these patients and compare them with the literature data . Due to paracoccidioidomycosis is another neglected disease in Latin American countries, the present report is very important in order to elucidate what is the real magnitude of this mycosis in the context of HIV infected individuals. Currently there is a great scientific interest to define if PCM can be added to the list of opportunistic diseases which define AIDS and its clinical presentation would be considered as another clinical form named mixt by some authors.

**********

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