Incidence and predictors of mortality among TB-HIV co-infected individuals on anti-tuberculosis and anti-retroviral dual therapy in Northwest Ethiopia: A retrospective cohort study

Abebe Fenta; Tebelay Dilnessa; Destaw Kebede; Mekuriaw Belayneh; Zigale Hibstu Teffera; Bewket Mesganaw; Adane Adugna; Wubetu Yihunie Belay; Habtamu Belew; Desalegn Abebaw; Bantayehu Addis Tegegne; Zelalem Dejazmach; Fassikaw Kebede; Gashaw Azanaw Amare

doi:10.1371/journal.pone.0337612

Peer Review History

Original SubmissionMay 22, 2025
3 Sep 2025 Decision Letter - Shiv Sah, Editor Dear Dr. Fenta 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. Please submit your revised manuscript by Oct 18 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. 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 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, Shiv Kumar Sah, Master 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. In the online submission form you indicate that your data is not available for proprietary reasons and have provided a contact point for accessing this data. Please note that your current contact point is a co-author on this manuscript. According to our Data Policy, the contact point must not be an author on the manuscript and must be an institutional contact, ideally not an individual. Please revise your data statement to a non-author institutional point of contact, such as a data access or ethics committee, and send this to us via return email. Please also include contact information for the third party organization, and please include the full citation of where the data can be found. 3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 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? Reviewer #1: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: No Reviewer #2: Yes ****** Reviewer #1: Comments to the author There are typographical and grammatical errors that need to be corrected throughout the document The retrospective nature of the study might pose incomplete registration and losing of important variables. Was the registry you accessed were complete for all variables , how do you manage incomplete data In your study being male were an important predictor mortality. What is the implication behind this finding Abbreviation is not recommended in the abstract section of an article, please remove any abbreviations in the abstract In your finding you reported that the ‘The mortality rate among TB-HIV co-infected patients at Debre Markos Comprehensive Specialized Hospital was high’ what is your reference to say this number is big In survival analysis, the median survival time is the preferred statistical test, reporting mean might be misleading In your survival time description, there is no indications that censored observations were appropriately counted, which is critical in survival analysis Reviewer #2: 1. Give proper format of Abstract. Reframe it properly. 2. The manuscript needs extensive revision for language and grammar. Avoid using personal pronouns. 3. Fig 1, Fig 2 & Fig 3 needs proper explanation. 4. It is recommended to attach the questionnaire format. 5. The literature review may be rewritten to highlight comparisons with existing approaches. 6. Explain the proposed method thoroughly, incorporating the scenario to illustrate the work done. 7. Suggested to increase the data size. 8. Results section can be added and the practical limitation in the proposed methodology should be discussed in the results section. 9. It would be beneficial to include a graphical representation of the table for better understanding. 10. Authors are suggested to provide a comparative analysis to find the merit and demerit of existing and proposed methods. 11. Follow the format for references. ****** 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.] 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 Attachments Attachment Submitted filename: Comments to the author.docx Attachment Submitted filename: TB-HIV Comments.docx https://doi.org/10.1371/journal.pone.0337612.r001
Revision 1
17 Oct 2025 Author Response Point-to-point response to reviewers (Reviewer 1 &2) Many thanks for your valuable comments; all the review comments were followed, and revisions in the revised version of the manuscript were highlighted through track change. Point-to-point response to reviewer 1 Many thanks for your valuable comments; all the review comments were followed and made revisions in the revised version of the manuscript through track changes. The point-to-point replies are listed below: Comment 1: Give proper format of Abstract. Reframe it properly. Response1: Thank you very much for your comments. Yes, we agree with your comments, and a revision has been made. The Abstract has been thoroughly revised and structured according to the standard scientific format. It now includes Background, Objective, Methods, Results, and Conclusion and Recommendation sections. The content has been reframed for clarity, conciseness, and alignment with the study objectives and key findings. Comment 2: The manuscript needs extensive revision for language and grammar. Avoid using personal pronouns. Response2: Thanks a lot. We accept your comment, and a revision was made through track changes in the main manuscript. We carefully revised the entire manuscript for grammatical accuracy, sentence structure, and academic tone. All personal pronouns (e.g., we, our, us) have been removed or replaced with neutral and formal alternatives to maintain objectivity. Comment 3: Fig 1, Fig 2 & Fig 3 needs proper explanation. Response 3: Thanks again, and it has been revised based on your comment. Thus, the figures are well stated in the results section. All figures have been revised with clear explanations. • Figure 1 shows the overall Kaplan–Meier survival curve, indicating a gradual decline in survival among TB–HIV co-infected individuals over time. • Figure 2 compares survival by sex, showing lower survival probability among males. • Figure 3 compares survival by functional status, with bedridden patients having the poorest survival outcomes. Comment 4: It is recommended to attach the questionnaire format. Response 4: Thank you for your concern. The questionnaire used for data collection has been added as Supplementary File 1 in the revised manuscript to enhance transparency and reproducibility. Comment 5: The literature review may be rewritten to highlight comparisons with existing approaches. Response 5: Thank you again for your valuable comments. The introduction emphasizes global and regional TB-HIV co-infection trends, mortality rates, and interventions, and clearly identifies gaps addressed by our study, particularly in the Ethiopian context. We have revised the introduction to better highlight comparisons with existing studies and approaches. Comment 6: Explain the proposed method thoroughly, incorporating the scenario to illustrate the work done. Response 6: Thanks. Corrected based on your comment in the main manuscript through track change (see under the ‘Data collection and quality control’. We have revised the Methods section to explain the study procedures clearly. This retrospective cohort study included all TB-HIV co-infected patients receiving dual therapy at Debre Markos Hospital between 2011 and 2020. Data was extracted from hospital registers using a structured pre-tested data extraction checklist. Comment 7: Suggested to increase the data size. Response 7: We appreciate the suggestion to increase the sample size. However, due to the retrospective nature of the study and the fact that the data were already collected, it is not possible to increase the sample size. We believe that the current dataset is sufficient to address the study objectives and provide meaningful results. Comment 8: Results section can be added and the practical limitation in the proposed methodology should be discussed in the results section. Response 8: Thank you for your suggestion. In the revised paper, we have modified it through track change (Please see in the Strengths and Limitations of the Research). Comment 9: It would be beneficial to include a graphical representation of the table for better understanding. Response 9: Thank you for the suggestion. However, due to the large size of the tables, presenting the data graphically is challenging. We believe it is clearer and more practical to retain the current tabular format. Comment 10: Authors are suggested to provide a comparative analysis to find the merit and demerit of existing and proposed methods. Response 10: We appreciate the reviewer’s suggestion. A comparative analysis of the existing and proposed methods has been added to highlight their respective merits and limitations. This addition clarifies the advantages of our proposed approach and provides a balanced evaluation relative to existing methods. Therefore, the discussion part was revised based on your comment. Comment 11: Follow the format for references. Response 11: We thank the reviewer for the comment. All references have been revised to follow the journal’s required format. Point-to-point response to reviewer 2 Many thanks for your valuable comments, all the review comments were followed and made revisions in the revised version of the manuscript highlighted through track change. The point-to-point replies are listed as bellows: Comment 1: There are typographical and grammatical errors that need to be corrected throughout the document Response 1: We appreciate the reviewer’s observation. The manuscript has been carefully revised for typographical and grammatical errors throughout to improve clarity and readability.The manuscript revised based on your comment through tack change. Comment 2: The retrospective nature of the study might pose incomplete registration and losing of important variables. Was the registry you accessed were complete for all variables , how do you manage incomplete data Response 2: We acknowledge this limitation. While the hospital registry was comprehensive for most key variables, some data was incomplete. We managed to lose the missing data by excluding incomplete records, and it has discussed this in the limitation section of the manuscript. Comment 3: In your study being male were an important predictor mortality. What is the implication behind this finding Response 3: The finding that male sex is an important predictor of mortality may suggest underlying biological, behavioral, or social factors that increase vulnerability. This observation emphasizes the need for targeted interventions and further research to understand sex-specific risk factors in TB-HIV co-infected patients. Comment 4: Abbreviation is not recommended in the abstract section of an article, please remove any abbreviations in the abstract Response 4: We thank the reviewer for the guidance. As mach as possible, the abbreviations have been removed from the abstract to ensure clarity and compliance with journal requirements. Comment 5: In your finding you reported that the ‘mortality rate among TB-HIV co-infected patients at Debre Markos Comprehensive Specialized Hospital was high’ what is your reference to say this number is big Response 5: We appreciate the reviewer’s comment. The statement has been revised to provide a comparison with national or regional TB-HIV mortality rates, supporting the claim with relevant literature. Comment 6: In survival analysis, the median survival time is the preferred statistical test, reporting mean might be misleading Response 6: We thank the reviewer for this important point. The manuscript has been updated to report median survival time, along with corresponding confidence intervals, in accordance with standard survival analysis practices. It was clearly stated in the result section (Within 42 (IQR: 0.5-89) months of the calculated median follow-up time). Comment 7: In your survival time description, there is no indications that censored observations were appropriately counted, which is critical in survival analysis Response 7: We appreciate the reviewer’s observation. We have clarified in the result section of manuscript that censored observations were appropriately accounted for in the survival analysis. As shown in Table 4, the descriptive statistics separately present survival times for both censored and death outcomes, indicating that censored cases were included and properly handled in the analysis. Additionally, Kaplan–Meier survival functions and Cox proportional hazards models were applied, both of which account for censored observations by design. This ensures that all participants contributed follow-up time until death or censoring occurred. Patient Status Continuous Variable Mean Standard deviation Min. Max. Median Q1 Q3 Death Survival time 16.04 18.83 1 83 7.5 2 24.75 Censored Survival time 47.37 28.87 0.5 89 53.5 18.25 75 Overall Survival time 42.48 29.78 0.5 89 42 13 71.75 Table 4: Descriptive statistics of continuous variables for TB-HIV co-infected individuals on anti-TB and antiretroviral dual therapy in western Amhara, Northwest Ethiopia Finally, we appreciate both of the reviewers’ insightful comments and believe that the revisions have greatly improved the manuscript’s clarity, structure, and scientific quality. We hope the revised version meets the expectations of the reviewers and editors. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0337612.r002
12 Nov 2025 Decision Letter - Shiv Sah, Editor Incidence and Predictors of Mortality among TB-HIV Co-infected Individuals on Anti-tuberculosis and Anti-retroviral Dual Therapy in Northwest, Ethiopia: A Retrospective Cohort Study PONE-D-25-25283R1 Dear Dr. Fenta 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. For questions related to billing, please contact billing support . 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, Shiv Kumar Sah Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0337612.r003
Formally Accepted
Acceptance Letter - Shiv Sah, Editor PONE-D-25-25283R1 PLOS ONE Dear Dr. Fenta, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Mr Shiv Kumar Sah Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0337612.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .