PONE-D-22-13718AIDS Drug Assistance Program Disenrollment is Associated with Loss of Viral Suppression beyond Differences in Homelessness, Mental Health, and Substance Use Disorders: An Evaluation in Washington State 2017-2019PLOS ONE

Dear Dr. Erly,

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 manuscript has been evaluated by two reviewers, and their comments are available below.

The reviewers have raised concerns regarding the reporting and methodology of this study. 

Could you please revise the manuscript to carefully address the concerns raised?

Please submit your revised manuscript by Feb 27 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,

Johannes Stortz

Staff 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 your ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them.

3. Thank you for stating in your Funding Statement:

“JCD and CMK's work was supported by the University of Washington / Fred Hutch Center for AIDS Research, an NIH-funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. https://depts.washington.edu/cfar/?q=home”

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[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: Yes

Reviewer #2: Yes

**********

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 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

**********

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: 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: Thank you for the opportunity to review. The authors provide a careful analysis of changes in HIV viral suppression after disenrollment from Washington State’s AIDS Drug Assistance Program. The findings are directly relevant to policy, following the October 2021 removal of federal requirements that clients recertify every 6 months. The writing is clear and the quantitative bias analysis using the MMP data enhances the results. I have a few suggestions for the authors as they revise their work.

First, please add a “Table 1” of descriptives of the main study sample. Some of this information is in Supplementary Table 1. I recommend moving that to the main text and adding a column to provide descriptives on the full sample. In the Supplementary Table 1, the prevalence ratio is less intuitive for illustrating the differences between the two groups. As your reader, I am unsure how to interpret this column to quickly understand how characteristics differ between groups. Is there an easier way to present p-values showing differences between groups? If you prefer this format, please explain in the footnote and text how to interpret.

Second, I recommend a flow chart or other visualization to explain the sample design. Starting on line 136, the authors explain that each client contributed one recertification opportunity. If recertification were required every 6 months during the study period (per federal rules in place during the 2017-2019 study period), a client could potentially contribute multiple observations. It would be useful to have a better understanding of the time period of the study (are most observations from 2017 in the initial event?) and explanation for only considering one observation per study participant.

Third, a challenge with the HIV VL data is that in practice, VL testing is not always done precisely every 6 months. The VL tests can be missing for multiple reasons: falling out of care (which the authors code as not virally suppressed), having the tests done out of state and not reported to Washington’s surveillance system (for example, for persons who spend winter months in a different state), or because the patient is stable on their medications thereby receiving less frequent VL testing than the clinical guidelines (a comment I have heard anecdotally from clinicians). The authors already have a sensitivity analysis that excludes participants without a VL measurement before or after recertification. It would be useful to have more details on the timing of VL measurements in the data such as the percent of participants with 1+ or 2+ VL tests per year, the average and range in the time in between disenrollment & recertification events and VL testing, and comparison of sub-populations with and without regular VL testing. Please also discuss in the limitations how the timing of VL tests in relation to the time of recertification & disenrollment events might bias findings.

Reviewer #2: In this manuscript, the authors link data from the Washington State ADAP program with Washington State HIV surveillance data to understand the impact of disenrollment on viral suppression among ADAP enrollees between 2017 to 2019. They found that disenrollment was associated with a 12% decrease in viral suppression compared with continuous ADAP enrollment. They also found differences in the change in viral suppression by insurance status, with dual Medicare-Medicaid beneficiaries and those with “other public insurance” the most affected by disenrollment. Based on their findings, they conclude that disenrollment negatively impacts viral suppression and that simplifying or eliminating ADAP recertification may help to improve viral suppression among ADAP enrollees.

This is a well-written paper using unique datasets to answer an important policy question: what is the effect of ADAP disenrollment on viral suppression in Washington State? This question has not been addressed in the literature to date, making this both a unique and timely paper given the removal of federal requirements for ADAP client recertification in October 2021.

Major comments:

1. I appreciate the use of the risk difference to quantify the attributable risk of viral suppression due to lack of recertification. This is not used often enough for population-based studies such as this one.

2. Methods, lines 84-87: The inclusion criteria as described for this study is a little confusing. How is it known whether a client lives in Washington State for 12 months after leaving ADAP if they drop out of care? Is there active follow-up of those who drop out? Since this analysis uses surveillance data, it would seem that the residency status (Washington residence versus another state) of someone who disenrolls and does not have any contact with the providers in Washington State for over a year would be difficult to ascertain.

3. In addition to the important message about disenrollment and viral suppression, there may be a message about ineligibility and viral suppression worth mentioning in the Discussion, since those who became ineligible for ADAP also had substantial decreases in suppression (albeit in a smaller subset). However, some additional context may be necessary to better understand this (see my minor comment #1 below).

4. The comment in the Discussion that Washington is a Medicaid expansion state is an important one given that the inferences identified here could be exacerbated in a non-Medicaid expansion state. In fact, based on Table 1, “other public insurance” is the second largest group after “private insurance”. Can the authors clarify what type of insurance this is? Is it mostly Medicaid beneficiaries?

Minor comments:

1. Is there information on what the reasons for disenrollment and/or ineligibility among ADAP enrollees in Washington State, and how they are distributed? E.g., how often do ADAP clients lose eligibility because they obtain health insurance through a new job? Some context may be helpful to include in the Discussion if this information is available (although it may not be available).

2. Introduction, first sentence: The authors state that ADAPs are “a critical part of federal plans to reduce HIV incidence by 90% by 2030”. One assumes that this is because of the concept of “treatment as prevention” – this could be made clearer.

3. Introduction, line 60: The authors note that “individual programs now have the authority to modify the recertification requirement”. It would be helpful to insert the word “state” before the word “programs” to clarify and emphasize that ADAPs are administered by states.

4. Methods, line 107: if multiple VLs are recorded for a client before and after recertification opportunities, which ones are used in the analysis?

5. Methods, line 108: the word “is” is missing after “Viral suppression”

6. Methods, line 109: the word “of” is missing after “reduced risk”

7. Methods, line 156: consider replacing the word “estimate” with “estimand”

8. Methods, lines 171-172. Please clarify whether national or Washington State MMP data were used to estimate the bias parameters.

**********

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.

PONE-D-22-13718R1AIDS Drug Assistance Program Disenrollment is Associated with Loss of Viral Suppression beyond Differences in Homelessness, Mental Health, and Substance Use Disorders: An Evaluation in Washington State 2017-2019PLOS ONE

Dear Dr. Erly,

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 manuscript has undergone a thorough evaluation by two reviewers, and their comments are provided below. While the reviewer’s feel that most of their comments from the previous revision has been addressed there were some mathematical inconsistencies in the numbers reported within the tables of the Results section. We recommend thoroughly checking the numerical values for a accuracy.

Please submit your revised manuscript by May 20 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,

Lucinda Shen, MSc

Staff 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.

[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 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

**********

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: No

Reviewer #2: No

**********

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 addressed all reviewer comments. The manuscript is clear, technically sound, and well executed. The authors do not make their data publicly available but it is surveillance data and likely cannot be shared publicly.

Reviewer #2: I appreciate the efforts that the authors made to address my comments. I note a few minor issues in the revised version that should be fixed.

1. Results section: The overall eligible N of 5237 does not match the sum of the component categories (1336 disenrolled, 896 ineligible, 3006 continuously enrolled). It is off by 1. Should the N be 5238?

2. Table 1: The “race” category should be changed to “race/ethnicity” since Hispanic is an ethnicity, not a race.

**********

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.

AIDS Drug Assistance Program Disenrollment is Associated with Loss of Viral Suppression beyond Differences in Homelessness, Mental Health, and Substance Use Disorders: An Evaluation in Washington State 2017-2019

PONE-D-22-13718R2

Dear Dr. Erly,

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,

Dario Ummarino, PhD

Senior Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: