PONE-D-24-47069Longitudinal trajectories of sexual behavior and incident hepatitis C reinfection among men who have sex with men with HIVPLOS ONE

Dear Dr. Hage,

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.

While the findings are intriguing, reviewers have raised concerns regarding the public health implications of these classifications, particularly the lack of targeted intervention strategies. Additional reflection on how these findings can inform or advance public health interventions is necessary. Furthermore, reviewer have raised concern about the data being too old to be relevant at the current time. The authors need to address this issue, and if possible, add recent data to improve study relevance. Finally, reviewers have suggested a number of minor but important revisions to improve clarity, consistency, and precision throughout the manuscript. These suggestions include enhancing the presentation of numerical data, addressing methodological and analytical ambiguities, and elaborating on study limitations.

Please submit your revised manuscript by Apr 13 2025 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 academic editor and reviewer(s). 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,

Syed Hani Abidi

Academic Editor

PLOS ONE

Journal requirements: 

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf .

2. Your abstract cannot contain citations. Please only include citations in the body text of the manuscript, and ensure that they remain in ascending numerical order on first mention.

3.  Thank you for stating the following financial disclosure:

 [This work was supported by the “Aidsfonds” Netherlands (grant numbers 2008.026, 2013.037), the Netherlands Organization for Health Research and Development (ZonMw) (grant number 522004006) and GGD research funds.]. 

Please state what role the funders took in the study.  If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.""

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. Thank you for stating the following in the Competing Interests section:

[I have read the journal's policy and the authors of this manuscript have the following competing interests: J. S.’s institution has received research support and consultancy fees from Gilead, and a speakers fee from Janssen Pharmaceuticals, independent from the submitted work. M. P.’s institution has received speakers fees and independent scientific support from Gilead Sciences, Roche, MSD, and Abbvie, outside the submitted work. M. V.’s institution has received consultancy fees from Gilead, MSD and ViiV outside the submitted work and research grants from Gilead, Merck Sharp Dome and ViiV, A.B. has received a speakers fee from Gilead Sciences, independent for the submitted work, grants from MSD and Gilead Sciences, and participated in advisory boards and received travel support from MSD, Janssen-Cilag, Bristol-Myers Squibb, Gilead Sciences, Pfizer, and ViiV Healthcare, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.].

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

5. We note that you have indicated that there are restrictions to data sharing for this study. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

Before we proceed with your manuscript, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see

https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible.

We will update your Data Availability statement on your behalf to reflect the information you provide.

6. In the online submission form, you indicated that [Data are available upon reasonable request from the Principle Investigator (M. Prins, mprins@ggd.amsterdam.nl).].

All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information.

This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval.

7. 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. 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: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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: Even though this manuscript is quite interesting, this data is too old to be relevant at the current time. Also, a global pandemic happened, which impacted every aspect of life, including public health risks and interventions.

From as old as 15 years and as early as six years is too long a time.

Reviewer #2: This is an interesting paper that using LCA has identified two classes of MSM with distinctive patterns of behavioral risk whose HCV reinfection risk diverged after 3 years of follow up. The main problem with this paper is what is the advantage for public health interventions of using the classification of MSM versus focusing on risk behaviors, given that the authors do not suggest targeted interventions but "frequent behavioral assessment is needed during care and should be extended over the years following HCV clearance". A further reflections on these implications is necessary for a recommendation for publications.

Reviewer #3: This study presents an analysis of hepatitis C reinfection in a cohort of gay, bisexual, and other men who have sex with men living with HIV in Amsterdam, elucidating risk factors for hepatitis C transmission in this high-risk group. It is well written, innovative in focusing on this target population, and employes rigorous statistical methods to gain a deeper understanding of this phenomenon. The key limitations, including a small sample size and limited generalizability are acknowledged. I have only a few suggestions, as below, and otherwise congratulate the authors on their excellent work.

• Abstract. Here and elsewhere in the manuscript, where there are ranges of proportions presented, it would be more clear for the reader to include a % sign for both numbers in the range, as in “95%CI=11%-35%.” Consider spaces before and after the equal sign, as it seems there is enough room.

• Abstract. In presenting the class 1 and class 2 results, please maintain the same order of the classes throughout, presenting first for C1 and then for C2. It would also be more clear to use consistent punctuation here and elsewhere in the manuscript, either “C1, result” or “C1: result.” Please be sure to add a space after the comma or colon. The numbers are very dense and needlessly run together.

• Introduction, lines 73-74. I would suggest “in 2014” since the verb is became and that happens only once. The alternative would be “have been widely available…since…”

• Introduction, lines 80-83. Important information is given about primary and reinfection rates that is left very vague, with no number presented. Please present numeric estimates of the primary and reinfection rates and the proportion of HCV incident cases from the reference cited.

• Methods, lines 123-124. The question about gloves was apparently not very clear. If participants were asked “Were gloves used during fisting or were gloves shared?” then a yes response could either mean that gloves were used or that gloves were shared. Was there any way to tell if gloves were used but not shared?

• Methods, lines 161-162. “The incidence rate (IR) per 100 person-years (PY) of HCV reinfection and its corresponding 95% confidence interval (CI) was analyzed” – the verb should be “were analyzed” since there are two subjects.

• Discussion, line 291. NAD has not been established as an abbreviation and is not used again. Please spell out.

• Discussion, lines 300-301. Please add “an” before “individual’s sexual network.”

• Discussion, line 303. Please correct “prevention programs…was delivered.”

• Discussion, line 307. Please change “in demographic and clinical characteristics” to in demographic or clinical characteristics.”

• Discussion, lines 311-312. Do the prior studies show younger age and lower CD4 counts to be potential determinants? Please be more specific about the direction of this association seen in other studies.

• Discussion, limitations. It could be more clearly stated that the small sample size and relative low number of events were key limitations. For latent class analysis, 250-300 or more is often mentioned as a minimum sample size.

• Discussion, lines 354-356. Consider adding “in other settings or circumstances” to the end of this sentence.

• Discussion, limitations. Reliance on self-reported behaviors and the potential for bias impacting results is not mentioned.

• Discussion, limitations. Consider referring to PMID: 36398215 and discussing how different approaches to modeling risk over time can have important impact on results in latent class trajectory studies and therefore the results should be considered to be hypothesis-generating and should be confirmed in other studies.

• Table 1. There is a footnote about p values and yet no p values are presented in this table. Please add these, as the comparisons are helpful and p values are included in the other comparison table (Table 2).

**********

6. 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: Yes:  Arshad Altaf

Reviewer #2: No

Reviewer #3: 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.

Longitudinal trajectories of sexual behavior and incident hepatitis C reinfection among men who have sex with men with HIV

PONE-D-24-47069R1

Dear Dr. Hage,

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.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Syed Hani Abidi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

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 #2: Yes

Reviewer #3: Yes

Reviewer #4: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: 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 #2: This manuscript has improved after feedback from reviewers as the authors have made changes that clarify and resolve the issues that were suggested. I can recommend this manuscript for publication in this updated version.

Reviewer #3: This is a sound analysis and excellent contribution to the literature on risk factors for hepatitis C among men who have sex with men.

Reviewer #4: Authors have revised the manuscript as per reviewers' comments. One last comment, in the title of the manuscript, please add "of" after the word "incident".

**********

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 #2: No

Reviewer #3: Yes:  Susan M. Graham

Reviewer #4: No

**********