-->PONE-D-25-57826-->-->HIV, Nephrotoxic Medications, and Chronic Kidney Disease: Prevalence, Risk Factors, and Mediation Analyses Among People With and Without HIV in the Multicenter AIDS Cohort Study (MACS) / Women’s Interagency HIV Study (WIHS) Combined Cohort Study-->-->PLOS One

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Academic Editor

PLOS One

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The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange and Elizabeth Topper), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen, Audrey French, and Ryan Ross), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Claudia Martinez, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, James B. Brock, Emily Levitan, and Deborah Konkle-Parker), U01-HL146192; UNC CRS (M. Bradley Drummond and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institute on Aging (NIA), National Institute of Dental & Craniofacial Research (NIDCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1-TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30-AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), P30-AI-124414 (ERC-CFAR), P30-MH-116867 (Miami CHARM), UL1-TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA).

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Additional Editor Comments :

Thank you for this submission. Kindly attend to the comments from the reviewers, particularly paying attention to the methodological aspects. In the current state, this study is not clear enough to be repeatable by independent readers. A concise revision improving on what was done, how, and when on which group could drastically improve the manuscript.

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: No

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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: No

Reviewer #2: Yes

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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: No

Reviewer #2: Yes

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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: The manuscript titled "HIV, Nephrotoxic Medications, and Chronic Kidney Disease: Prevalence, Risk Factors, and Mediation Analyses Among People With and Without HIV in the Multicenter AIDS Cohort Study (MACS) / Women’s Interagency HIV Study (WIHS) Combined Cohort Study", is a timely highlight to the increase in non-AIDS comorbid conditions in people with HIV whose life expectancy has greatly improved following universal rollout of ART.

Major comments

1. It is not clear whether the current analysis was on one or on repeated measures. In the methods section, you note that visit 101 data was analysed, yet in the statistical modeling, results, and discussion, there are mentions of repeated measures.

2. Please clarify why visit 101 was chosen as "baseline".

3. It would be important to clarify how the bidirectional relationships between CKD and depression, nephrotoxic medications and CKD, and hypertension and nephrotoxic medications were modeled.

4. It is not clear how nephrotoxic medications, hypertension, diabetes, etc were defined, and misclassification was minimized, or by how much did it affect the results?

5. What is the reliability and consistency of CES-D in the identification of depression in people with HIV?

6. The selected sample is not the entire MWCCS; presumably, there was missingness of key variables. How did the selection bias affect the results?

Minor

1. The text is sparsely referenced, yet there is a plethora of literature about HIV, CKD, nephrotoxicity, and depression.

2. Please use consistent word tense; in some places past tense is used and in others present tense.

3. What measures of kidney function indicated worse outcomes among the PLWH ? The outcomes are not stated in the methods.

4. Please clarify what is meant by "other individuals" in the statement "Among marital categories,

widowed and “other” individuals exhibited elevated CKD rates" found in the first paragraph of page 9.

In the same page, please clarify what you meant by "non-Hispanic Other individuals"

Reviewer #2: This manuscript addresses an important and clinically relevant question regarding the relationships among HIV serostatus, depression, nephrotoxic medication use, and chronic kidney disease (CKD) within the MWCCS cohort. The topic is timely, and the dataset is rich. I commend the authors for this manuscript. However, several methodological and interpretive issues require clarification before the findings can be fully evaluated. Strengthening the transparency of the analytic approach and improving the organization of the manuscript would substantially enhance its clarity and scientific contribution. Further details for the authors to revise or clarify are in the attached review.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-25-57826_Review.docx

HIV, Nephrotoxic Medications, and Chronic Kidney Disease: Prevalence, Risk Factors, and Mediation Analyses Among People With and Without HIV in the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study

PONE-D-25-57826R1

Dear Dr. Pan,

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.

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Kind regards,

Tinei Shamu

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: All comments have been addressed

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: No

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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

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 of the manuscript have answered all queries appropriately, and there are no additional questions.

Reviewer #2: The manuscript addresses an important topic. All comments from the previous review have been adequately addressed.

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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

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