PONE-D-19-35988

Tuberculin skin test positivity among HIV-infected alcohol drinkers on antiretrovirals in south-western Uganda

PLOS ONE

Dear Dr. Muyindike,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

Reviewer #2: No

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4. 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

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. General comment: This manuscript generally adds to the body of knowledge on issue of LTBI. The authors need to explain the policy implications of their results given TB preventive therapy (TPT) is being recommended for all people with HIV. At a prevalence of 27.5% in the study population, do we seem to be recommending to 72.5% that do not need it. Or it is also possible that the 72.5% had not yet mounted a good immune response to reflect positivity?

2. Line 56: The authors should reference the latest global TB report (2019)

3. Line 64: Authors advised to cross check the latest incidence. It has come down lately

4. Line 166: Authors should indicate the IRB approval numbers

5. Line 173: The breakdown of the participants screened doesn’t total up to 106. Totals up to 118

6. Line 177: 418 minus total excluded= 300 not 312. Authors should crosscheck these figures in the section 172-181

7. Tables 2 and 3: The authors need to explain why they included all the factors in the multivariate analysis yet they were insignificant at bivariate? If these had biological plausibility, then they need to mention it and provide the appropriate references

8. Lines 226-237: Paragraph is too long. Could be split into 2 i.e. prevalence of LTBI and then the paragraph on odds of TST positivity given alcohol use history. The authors need to explain why there was no association between TST positivity among HIV infected current alcohol users and yet literature shows alcohol consumption is a big risk factor for TB. Is it possible that the TB among alcohol users is the primary TB instead of reactivation?

Reviewer #2: The introduction and abstract were generally clear and readable. A minor stylistic note is not to report results that are not findings of the study without reference, Since it is not practise to reference in abstracts perhaps it would be useful to say “there is evidence to suggest alcohol users have an increased risk of developing disease...” {leave it in intro line 72} There is a clear outline of the aim and synopsis of what is known and what is not known this is good. The purpose and hypothesis are also clearly defined. In the Methods section eligibility and sample are well described. The reliability and validity of using TST as a primary instrument are described in the discussion but should appear in the methods. It would be useful to have the complete definitions for “prior unhealthy” consumption. Systematic bias maybe introduced by only including TST screened for LTBI prevalence estimate. TST. There may be a potential systematic reason why these people did not present (too ill/heavy drinkers). The result tables are clear and readable. There is no stratification by alcohol use, the independent variable, it is an all or nothing measure. Therefore, the evidence is not sufficient for conclusions drawn in line 245 -247{This may suggest that alcohol use may be playing a lesser role in acquiring TB infection among PLWH on ART, compared to its role in TB disease progression}. These are merely measuring of association the lack of sample decreased the statistical value of these measures. For example, men report drinking (87%) but there are less men are in the study (37%). Drawing any links between alcohol use and TST response seem tenuous at best.

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Reviewer #1: No

Reviewer #2: 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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-35988R1

Tuberculin skin test positivity among HIV-infected alcohol drinkers on antiretrovirals in south-western Uganda

PLOS ONE

Dear Dr. Muyindike,

Thank you for submitting your manuscript to PLOS ONE. We provisionally accept the manuscript, but would like to give you the opportunity to address the final minor comments raised by the reviewer. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Jun 26 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable 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. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled '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.

We look forward to receiving your revised manuscript.

Kind regards,

Nicky McCreesh

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

Reviewer #2: 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

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: Line 31: Comments have been addressed, but I would still add “….current evidence…”

Line 131-136: Comments have been addressed, but phrasing is still in discussion form, maybe best to some of it in the discussion as a limitation of this work.

(line 131) “TST may not be a perfect test for LTBI but it is widely accepted as a reasonable proxy [28] and”

AND

(line 134) “Both tests perform reasonably well in high-TB burden settings and correlate well with proxy measures of exposure [28].” I would move back to discussion and expand.

I would also move the sentences around in the method section (line 134/5) “TST may have reduced sensitivity in immune-compromised individuals such as… “ before the sentence starting (line 130) “A TST…”

281-285 comments have been addressed, but I would leave out (line 286) “However, the exclusions do not introduce a systematic bias that we see.”

line 245 -247 comments were addressed.

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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

Reviewer #2: 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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Tuberculin skin test positivity among HIV-infected alcohol drinkers on antiretrovirals in south-western Uganda

PONE-D-19-35988R2

Dear Dr. Muyindike,

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,

Nicky McCreesh

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: