PONE-D-21-34754Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV; A systematic review and meta-analysis protocolPLOS ONE

Dear Dr. Frank Mulindwa,

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Surasak Saokaew, PharmD, PhD, BPHCP, FACP

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

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Reviewer #1: This is an important study and the manuscript reads well. Overall it is technically sound. I did have a number of queries and considerations which may be pertinent.

1. Could the authors explain how they will account for prior ART exposure, and previous ART regimens

2. The period of study is over a large time period January 2000 to May 2021. There have been several clinical management developments during this time which may have a bearing. Have the authors considered this and might a shorter time period of review be more advantageous in this respect.

3. It is difficult to define a priori sub group analysis but some ideas of potential areas may enhance the protocol. Amongst this geographical and ethnic subgroups might provide useful insights.

Reviewer #2: It's an interesting study. There are no studies evaluating the association between Integrase inhibitor and diabetes or insulin resistance.

The authors should use official abbreviation for drug group name.

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Reviewer #1: No

Reviewer #2: No

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Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV: A systematic review and meta-analysis protocol.

PONE-D-21-34754R1

Dear Dr. Frank Mulindwa

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Surasak Saokaew, PharmD, RPh, PhD, BPHCP, FACP, FCPA

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: