Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patients

Edwin Eliel Escobar-Guevara; María Esther de Quesada-Martínez; Yhajaira Beatriz Roldán-Dávila; Belkisyolé Alarcón de Noya; Miguel Antonio Alfonzo-Díaz

doi:10.1371/journal.pone.0285976

Peer Review History

Original SubmissionMarch 18, 2022
23 May 2022 Decision Letter - Eliseo A Eugenin, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-22-08134Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patientsPLOS ONE Dear Dr. Escobar, 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. The data is exciting, however, the presentation is not well done and the interpretation is also compromised. Please answer all the issues. These article types are not expected to include results but may include pilot data. Please submit your revised manuscript by Jun 30 2022 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, Eliseo A Eugenin, Ph.D. 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. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. 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Upon resubmission, please provide the following: The name of the colleague or the details of the professional service that edited your manuscript A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a supporting information file) A clean copy of the edited manuscript (uploaded as the new manuscript file) 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access We will update your Data Availability statement to reflect the information you provide in your cover letter. [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: N/A ****** 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 ****** 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: No Reviewer #2: 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: The authors aim to investigate to neurocognitive impairment in individuals co-infected with HIV and Toxoplasma gondii. The study is straight forward and included the corresponding controls. However, there are problems associated to the organization and presentation of the data. The project would benefit of the following recommendations: 1. English language needs substantial revision. 2. Each graph should present every single subject on each bar graph. Also, the statitistical analyses need to be robust since this reviewer is skeptical that several comparisons are significant due to the high variability. 3. The manuscript needs standard submission organization. For example, each result subsection should state the main findings and each figure needs to include all the graphs for that specific figure (e.g., A, B, C,... F). Please see how other papers published in the journal are organized. 4. The discussion is really long and an iteration of the results. Therefore, please reduce it, eliminate figure labels in the discussion, summarize each result and compare it to other studies in the area. Reviewer #2: In abstract session: • For expression significantly, should be mention p-value. • Statistical tests and software used for data analysis are mentioned. In introduction session: • The aim of the study should be clearly explain. In methods session: • Mention the study time. • Mention the software used to analyze the data and its version. • Mention the ethics code. In results session: • In some diagrams, did not mention the horizontal axis title. • Abbreviations (C1, P1A, etc.) should be written in full below the image. ****** 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: 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. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: PONE-D-22-08134.docx https://doi.org/10.1371/journal.pone.0285976.r001
Revision 1
12 Sep 2022 Author Response Response to Editor and Reviewers: 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Answer: We have revised the entire document, trying to meet PLOS ONE's style requirements, including those for file naming. 2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. Upon resubmission, please provide the name of the colleague that edited your manuscript. Answer: We were kindly assisted by a colleague in California, who prefers to remain anonymous, to read and proofread the entire manuscript, providing valuable suggestions for improvement. 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. Answer: The data set used to reach the conclusions drawn in this manuscript is provided in S2-7 Tables (see Supporting Information). Two-tailed T-student or Mann-Whitney tests, as appropriate, were used to compare groups. Pearson product moment was used to analyze correlation. S8 Table provides medians, 25th and 75th percentiles for cytokines values. S9-14 Tables provides all particular p-values. Data in S2-7 Tables were used to build graphs. 4. Is the manuscript technically sound, and do the data support the conclusions? a. Reviewer #1: Partly Answer: We are providing additional Tables to explain how data were analyzed, and we hope that this additional information could show how data support the conclusions b. Reviewer #2: Yes 5. Has the statistical analysis been performed appropriately and rigorously? a. Reviewer #1: No Answer: We modified the presentation of results, showing p-values for statistically significant results, and provide S9-14 Tables with all particular p-values, including information about the method used and the power of performed test. We hope that this additional information could help to explain that statistical analysis has been performed appropriately and rigorously. b. Reviewer #2: N/A 6. Have the authors made all data underlying the findings in their manuscript fully available? a. Reviewer #1: Yes b. Reviewer #2: Yes 7. Is the manuscript presented in an intelligible fashion and written in Standard English? a. Reviewer #1: No Answer: We have thoroughly copyedited our manuscript for language usage, spelling, and grammar. We were kindly assisted by a colleague in California, who read and edited the entire manuscript. b. Reviewer #2: Yes 8. Review Comments to the Author a. Reviewer #1: The authors aim to investigate to neurocognitive impairment in individuals co-infected with HIV and Toxoplasma gondii. The study is straight forward and included the corresponding controls. However, there are problems associated to the organization and presentation of the data. The project would benefit of the following recommendations: i. English language needs substantial revision. Answer: As we have mentioned before, we have thoroughly copyedited our manuscript for language usage, spelling, and grammar. A colleague in California read and copyedited the manuscript. ii. Each graph should present every single subject on each bar graph. Also, the statistical analyses need to be robust since this reviewer is skeptical that several comparisons are significant due to the high variability. Answer: We have modified graph presentation, including every single patient’s value as black dots. We provide every single p-value (S9-14 Tables), including information about the method used and the power of the performed test. We hope that this additional information could explain that statistical analysis has been properly performed. iii. The manuscript needs standard submission organization. For example, each result subsection should state the main findings and each figure needs to include all the graphs for that specific figure (e.g., A, B, C... F). Please see how other papers published in the journal are organized. Answer: We have revised the entire document, trying to meet PLOS ONE's style requirements. We have modified the presentation of results, stating the main findings, showing p-values for statistically significant results and providing all particular p-values (S9-14 Tables). Figures presentation has been also modified. iv. The discussion is really long and an iteration of the results. Therefore, please reduce it, eliminate figure labels in the discussion, summarize each result and compare it to other studies in the area. Answer: We have revised and modified discussion, eliminating figure labels, summarizing results and comparing with other studies. We have tried to reduce it, avoiding iteration, but trying to discuss all the important issues. b. Reviewer #2: i. In abstract session: 1. For expression significantly, should be mention p-value. Answer: p<0.05 was considered as significant (see Abstract, page 3, line 48). We modified the presentation of results, showing p-values for statistically significant results. All particular p-values are provided in S9-14 Tables. 2. Statistical tests and software used for data analysis are mentioned. Answer: Groups were compared using T-student or U-Mann-Whitney tests as appropriate (see Abstract, page 3, line 48). Software used to perform statistical analysis of data was SigmaStat® for Windows, Version 1.0 (1992-1994 Jandel Corporation) (see Statistical analysis, page 13, lines 240, 241) ii. In introduction session: 1. The aim of the study should be clearly explain. Answer: The aim of the study was to evaluate how T. gondii-specific response changes in different stages of the HIV-1 infection, and if this change could be associated with modifications in neurocognitive functions. Immune response was assessed by studying cytokine production in response to T. gondii antigens, and neurocognitive functions by evaluating auditory and visual P300 cognitive evoked potentials, Sternberg’s speed of memory scanning task and Wisconsin Card Sorting Test (see Introduction, pages 5 and 6, lines 91-94). iii. In methods session: 1. Mention the study time. Answer: Samples were analyzed and neurophysiological evaluations were performed between May 2007 and December 2009. Manuscript was written between August 2021 and February 2022. 2. Mention the software used to analyze the data and its version. Answer: SigmaStat® for Windows, Version 1.0 (1992-1994 Jandel Corporation) was used to perform statistical analysis of data 3. Mention the ethics code. Answer: All participants provided written informed consent and the study was approved by the ethic boards of the participating institutions, in accordance with the Declaration of Helsinki (1964-2013) and the Belmont Report (1979). iv. In results session: 1. In some diagrams, did not mention the horizontal axis title. Answer: Figures presentation has been revised and modified. 2. Abbreviations (C1, P1A, etc.) should be written in full below the image. Answer: Figures legends explain what abbreviations mean: HIV-1-non infected individuals that were seronegative (C1) or seropositive (C2) to T. gondii, and HIV-1 infected (P1) or HIV-1/T. gondii co-infected (P2) patients. Patients (P1 and P2) were grouped as early/asymptomatic or late/symptomatic, depending if their peripheral blood CD4+ T lymphocytes counts were higher (P1A and P2A) or lower (P1B/C and P2B/C) than 350/μL, respectively. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0285976.r002
28 Nov 2022 Decision Letter - Eliseo A Eugenin, Editor PONE-D-22-08134R1Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patientsPLOS ONE Dear Dr. Escobar, 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. ============================== Dear Dr. Escobar Thank you for submit your manuscript to PLOsone. The reviewers and I, feel that you did not include all the answers and changed the figures as requested. You and your team needs to include all the changes suggested Best Regards Eliseo Eugenin ============================== Please submit your revised manuscript by Jan 12 2023 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, Eliseo A Eugenin, Ph.D. Academic Editor PLOS ONE Dear Dr. Escobar Thank you for submit your manuscript to PLOsone. The reviewers and I, feel that you did not include all the answers and changed the figures as requested. You and your team needs to include all the changes suggested Best Regards Eliseo Eugenin [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed most of the comments raised in a previous round of review Reviewer #1: (No Response) Reviewer #2: ******** 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: Partly Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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: Yes 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: No 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: The authors should check the format of other PLoS One published papers and use similar format. Also, the results' presentation is boring. The authors should use the conclusions of each section as title of each result subsection instead of "Production of IL-10". Figure legends should be in their own subsection at the end of the manuscript in order instead of being inserted between the result section. The discussion for the results obtanied should not be longer than 4 pages long. Presently, the discussion is 8 pages long which is ridiculous. Please be succinct and avoid iteration of the results. Reviewer #2: They need to include the suggested changes 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.] 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. https://doi.org/10.1371/journal.pone.0285976.r003
Revision 2
28 Feb 2023 Author Response Response to Editor and Reviewers: Comments to the Author 1. If the authors have adequately addressed most of the comments raised in a previous round of review Reviewer #1: (No Response) Reviewer #2: ________________________________________ 2. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Partly Answer: We have revised the entire document, and made deep modifications in results and discussion sections. All data used to reach the conclusions drawn in this manuscript is provided. Tables are also provided to explain how data were analyzed, to show how data support conclusions. Reviewer #2: Yes ________________________________________ 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know Answer: We show p-values for statistically significant results, and provide S9-14 Tables with all p-values, including information about the method used and the power of performed test. This information explain that statistical analysis been performed appropriately and rigorously. ________________________________________ 4. Have the authors made all data underlying the findings in their manuscript fully available? Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 5. Is the manuscript presented in an intelligible fashion and written in standard English? Reviewer #1: No Answer: We kindly asked Laura Bartoli, MD, from Australia and other colleague from California, who prefers to remain anonymous, to read and proofread the entire manuscript. They provided suggestions for improvement. Reviewer #2: Yes ________________________________________ 6. Review Comments to the Author Reviewer #1: • The authors should check the format of other PLoS One published papers and use similar format. o Answer: We checked other PLoS One published papers to use a similar format in our manuscript. • Also, the results' presentation is boring. o Answer: we modified results section, to help reader to obtain the information easily. • The authors should use the conclusions of each section as title of each result subsection instead of "Production of IL-10". o Answer: We modified results section, stating the main findings of each subsection. • Figure legends should be in their own subsection at the end of the manuscript in order instead of being inserted between the result section. o Answer: we had followed the instructions given to authors in the Submission Guidelines document: “Figure captions Figure captions must be inserted in the text of the manuscript, immediately following the paragraph in which the figure is first cited”. (https://journals.plos.org/plosone/s/submission-guidelines#loc-figures-and-tables • The discussion for the results obtained should not be longer than 4 pages long. Presently, the discussion is 8 pages long which is ridiculous. Please be succinct and avoid iteration of the results. o Answer: we substantially reduced the length of discussion section to meet, as close as possible, the required four pages for discussion. Reviewer #2: • They need to include the suggested changes o Answer: we had made our best effort to include all suggested changes. Attachments Attachment Submitted filename: Response to Reviewers-Feb 2023.docx https://doi.org/10.1371/journal.pone.0285976.r004
7 May 2023 Decision Letter - Eliseo A Eugenin, Editor Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patients PONE-D-22-08134R2 Dear Dr. Escobar-Guevara, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Eliseo A Eugenin, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Dr. Escobar-Guevara Thank you for submit your corrections to PLOSone. My apologies for the extended time for an answer. Eliseo Eugenin 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 #1: 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 ****** 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) ****** 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 ******** https://doi.org/10.1371/journal.pone.0285976.r005
Formally Accepted
15 May 2023 Acceptance Letter - Eliseo A Eugenin, Editor PONE-D-22-08134R2 Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patients Dear Dr. Escobar-Guevara: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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. If we can help with anything else, please email us at plosone@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 Dr. Eliseo A Eugenin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0285976.r006

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