PONE-D-21-19756

Human T-Lymphotropic virus type 1 and Human Immunodeficiency Virus co-infection in rural Gabon

PLOS ONE

Dear Dr. Mouinga-Ondemé,

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.

Specifically some technical information (PCR methods, used ELISA, determination of the CD4 count) were missing and deserved to be described in material and method. More importantly, because of the cross-sectional approach a carefull description of the viro-immunological status (point 2 of the reviewer 1) and clinical status of the patient as well as sequence data for the HTLV (point 4 and suggestion of the reviewer 1) deserved to be provided as suggested by the reviewer 1. To note even if not obtained at the time of sampling, clinical data obtained thereafter but for all cases evaluated may provide a tast of longitudinal study.

Please submit your revised manuscript by Oct 08 2021 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Pierre Roques, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Please note that only a rewriting will not be sufficient to push up the article to publication. Additional data have to be included as requested by the two reviewers

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

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: No

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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: In this article by Mouinga-Ondemé et al, the prevalence of HTLV-1 infection was estimated at 7.7% in an HIV-infected population in south-eastern Gabon. Dually infected HIV + HTLV patients have so far been considered at risk of a faster clinical course to AIDS, but data are badly needed to support this hypothesis. Many studies have already been published but Gabon remains one of the right place to carry out such studies due to the superposition of both endemic.

This is of major interest to better understand the factors underlying the progression of HIV in patients infected with HLTV. Unfortunately, the cross sectional aspect of the data collect considerably limits the interest of this paper. The authors proposed that plasma viral load may be slightly lower and CD4 cell count higher in double-infected patients, but these data were not statistically significant.

In addition, before to be considered for publication, various questions remain:

1 / Inclusion criteria for the population infected with HIV in this study. Explain the unbalanced sex ratio. Over representation of the pregnant women ?

2 / EIA + but PCR negative and / or WB not known: additional molecular tests are absolutely necessary in this country with a high STLV / HTLV prevalence. Have you performed additional seological and molecular tests?

3 / The assays used for the RT-PCR viral load and the CD4 count must be specified (manufacturers?)

4 / Could we have more details about HTLV sequencing? Is the population only infected with HTLV-1 B?

5 / Clinical data concerning bi or mono infected patients are essential. HAM / TSP / ATTL reported in dually infected patients? Or more frequent neurological or haematological pathologies in this group?

The study is currently limited by the cross-sectional approach and the scarcity of biological and clinical data.

Suggestion to Authors: Despite the nucleotide diversity between HIV-1 and HTLV-1, their RT enzymes exhibit a fairly similar structure in the palm and fingers. All of these patients are (or have been) treated with 3TC / TFC and 184V and must certainly be present in HIV-RT in the majority of patients. A short sequencing of the HTLV RT pocket could be interesting because the intracellular level of lamivudine will lead to a selection of certain HTLV mutations; V118I and others have been proposed as relevant in explaining the high "resistance" of HTLV to 3TC in the 1980s. But recent interest in resistance to HTLV 3TC at least in vitro (DOI: 10.1086 / 322785) has shown that the question is still open. As the buffy coat was collected, sequencing could be easly performed. The presence of RT 3TC / FTC mutation (s) will confirm a potential replication of HTLV at the cellular level in this doubly infected population and will add original data to this article.

Reviewer #2: 480 / 5000

The article does not have sufficient consistency to support publication in Plos One.

Although the confirmation of HIV/HTLV-1 co-infection in patients from Gabon (Central Africa) is a serious public health problem, from a technical-scientific point of view the objectives are not clearly described, as well as the methodology and, furthermore, the results are insufficient for a publication in Plos One.

Therefore, I recommend that the article be submitted to another journal.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-21-19756R1Human T-Lymphotropic virus type 1 and Human Immunodeficiency Virus co-infection in rural GabonPLOS ONE

Dear Dr. Mouinga-Ondemé,

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 May 06 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 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,

Fatah Kashanchi

Academic Editor

PLOS ONE

Journal Requirements:

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.

Additional Editor Comments:

Please address the Reviewers comments

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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: (No Response)

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: (No Response)

Reviewer #2: Partly

**********

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

Reviewer #1: (No Response)

Reviewer #2: Yes

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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 Response)

Reviewer #2: Yes

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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 Response)

Reviewer #2: Yes

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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: Manuscript PONE-D-21-19756R1, Co-infection with human lymphotropic T virus type 1 and human immunodeficiency virus in rural Gabon is a descriptive cross-sectional study. The lack of clarity regarding the objectives and the lack of basic clinical data without any biological and clinical problems are major limitations to its publication in PlosOne

Despite these major limitations, given the importance of HIV / HTLV co-infection in public health and research and the paucity of studies, it is important to report these epidemiological data to the general public of PlosOne.

We suggest:

- improve the quality of the prevalence of coinfection data by matching the HIV HTLV population with the general population of the same place in the country in order to compare the prevalence of these two retroviruses in these different populations. This could at least lead to showing that the prevalence of HTLV, as expected, is higher in the HIV-infected population.

- and to make this article more attractive, we suggest that the discussion include a review of the literature on this double infection. A summary in the form of a table of epidemiological studies on HIV / HTLV co-infections which comment on the specific situation in Central Africa would be very necessary.

Reviewer #2: In this new version the manuscript presents sufficient consistency to support publication in the Plos One. However some modifications are necessary.

The title of the article sounds appropriate. However the data presented do not support the hypothesis the factors evaluated may favor the rapid evolution and progression to AIDS in HTLV-1/ HIV co-infected patients. This hypothesis must be reviewed since the corresponding author informed to reviewer #1 it is not possible to include new evaluations using the plasma and buffy coat.

Points to improve:

Line 100: Please define ART.

Line 114: Western Blot: please write Western with initial capital letter.

Line 130: Please define ANRS.

METHODS

The methodology should be described more organized and coherent. A good way is to insert subtitles:

1.Study design an population

2.HIV Viral Load and CD4 counts

3.HTLV diagnosis (include serological and molecular diagnosis. e.g.: serological diagnosis was performed..../ Molecular diagnosis was performed for all samples with a positive ELISA result. We extracted viral DNA from buffy-coat. )

4.HIV diagnosis

Line 150: The study was approved ...(It would be better moving this topic to the end of subtitle 1.: “Study design an population”

RESULTS

Patient Population: Please, describe the results in the order they appear in the table 1. This will make it easier for the reader to follow the data.

I suggest adding a bar graph figure of HTLV-1 prevalence PCR among men, women and total, according to the age groups evaluated.

DISCUSSION

It is important to review some points of the discussion after reviewing of the hypothesis that factors evaluated may favor the rapid evolution and progression to AIDS in HTLV-1/ HIV co-infected patients.

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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.]

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.

Human T-Lymphotropic virus type 1 and Human Immunodeficiency Virus co-infection in rural Gabon

PONE-D-21-19756R2

Dear Dr. Mouinga-Ondemé,

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,

Fatah Kashanchi

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 #1: (No Response)

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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: Partly

**********

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: (No Response)

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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

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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)

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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

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