PONE-D-20-05500

Health related quality of life of people receiving highly active antiretroviral therapy in Southwest Ethiopia

PLOS ONE

Dear Dr. Kefale,

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 Jul 13 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Haikel A. Lim, M.D., M.Sc.

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 noticed you have some minor occurrence of overlapping text with the following previous publication, which needs to be addressed:

https://phcfm.org/index.php/phcfm/article/view/294/html

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed."

3. Please address the following:

- Please describe how verbal consent was documented and witnessed.

- Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

4. Thank you for including your ethics statement:  This study was conducted after formal letter was requested and obtained from the department of Pharmacy, Mizan Tepi University. Then the permission to collect data was obtained after official letters were submitted to the head of ART clinic.

Please amend your current ethics statement to confirm that your named institutional review board or ethics committee specifically approved this study.

Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research.

Additional Editor Comments (if provided):

Thank you very much for your interest in submitting to PLOS One. The reviewers have raised valid points that I hope will be addressed in your revision of the manuscript.

In addition, please also address the following in your revision:

Please provide the participation rate for this study to better allow readers to appreciate the proportion of the sampling frame that agreed to review. This should also be included in the discussion as a limitation.

Please provide a reference for the QOL domain ranges of low/medium/high and the HAART score ranges of high/moderate/low adherence (page 6).

It is unclear if participants' pill counts were used or whether adherence was purely determined based on the MMAPS-8; please clarify.

Please spell out corrected and adjusted odds ratios before using the short forms (page 7).

Please highlight if all participants provided written informed consent, or if consent was waived (page 7).

The manuscript may benefit from another proof-read to correct the typographical and grammatical errors (e.g., the use of articles before nouns, etc.) throughout the manuscript.

[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: No

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: 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: This is a manuscript that assess the QoL of PLWHA who were taking HAART at MTUTH and identify factors associated with QoL. However there are some major concerns that i will hope the authors can address:

1. How is the sampling done? is it convenience of random? the duration of mar 4 to apr 1 is of concern as well. it is a little too short combined with convenience sampling, the type of patients surveyed may have a strong responder bias.

2. Is the patient reported outcome like MMAPS and WHOQOL-BREF validated in your country?

3. There is much more females than males. is the proportion accurate of your country pls?

Thank you for the opportunity to review. Happy to review again.

Reviewer #2: I have the following comments and happy to review this paper again.

1) Under the Introduction, the authors needs to discuss recent global landmark studies on HIV and QoL . Please add the following at the end of second paragraph of the Introduction.

..... largely dependent on cultural, social and environmental contexts as well as individual perception

(12,13). QOL has been used as a criteria in assessing HIV/AIDS prevention programs, clinical treatment, and harm reduction strategies (Vu et al 2020). Multilevel interventions and long-term care, rehabilitation, behavioral therapy and social supports for patients receiving treatments, and application of e-health approaches can improve QOL of HIV patients (Tran et al 2020).

References:

Vu GT, Tran BX, Hoang CL, et al. Global Research on Quality of Life of Patients with HIV/AIDS: Is It Socio-Culturally Addressed? (GAPRESEARCH). Int J Environ Res Public Health. 2020;17(6):2127. Published 2020 Mar 23. doi:10.3390/ijerph17062127

Tran BX, Vu GT, Ha GH, et al. Global Mapping of Interventions to Improve the Quality of Life of People Living with HIV/AIDS: Implications for Priority Settings [published online ahead of print, 2020 Feb 12]. AIDS Rev. 2020;1‐15. doi:10.24875/AIDSRev.20000135

2) Under the Introduction, the authors stated "ART may indeed prolong life but may only do so at considerable cost to the QoL of PLWHA (15)". This statement requires further elaboration.

... at considerable cost to the QoL of PLWHA (15). There is a geographical discrepancy in HIV/AIDS economic evaluation research (Tran et al 2019). The high cost of ART might reduce the adherence to treatment and worsen QoL (Tran et al 2020). An improved QoL and resultant ability of the patient to resume normal life..

References

Tran BX, Nguyen LH, Turner HC, et al. Economic evaluation studies in the field of HIV/AIDS: bibliometric analysis on research development and scopes (GAPRESEARCH). BMC Health Serv Res. 2019;19(1):834. Published 2019 Nov 14. doi:10.1186/s12913-019-4613-0

Tran BX, Hoang CL, Tam W, et al. A global bibliometric analysis of antiretroviral treatment adherence: implications for interventions and research development (GAPRESEARCH). AIDS Care. 2020;32(5):637–644. doi:10.1080/09540121.2019.1679708.

3) Under the discussion, the authors stated "The current study found that patients who ever used substances like alcohol, cigarette and khat (AOR=0.39, 95% CI=0.19-0.82) has less likely to have high global quality of life score

compared to those patients who never used substances." Please add the following statement:

... , cigarette and khat (AOR=0.39, 95% CI=0.19-0.82). While drug-related risk behaviors were significantly reduced, alcohol and sex-related behaviors remained risk factors for HIV (Tran et al 2019). Similarly, previous studies had also reported such findings......

Reference:

Tran BX, Fleming M, Nguyen TMT, et al. Changes in Substance Abuse and HIV Risk Behaviors over 12-Month Methadone Maintenance Treatment among Vietnamese Patients in Mountainous Provinces. Int J Environ Res Public Health. 2019;16(13):2422. Published 2019 Jul 8. doi:10.3390/ijerph16132422.

**********

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: Yes: Roger Ho

[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-20-05500R1

Health related quality of life of people receiving highly active antiretroviral therapy in Southwest Ethiopia

PLOS ONE

Dear Dr. Kefale,

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.

==============================

I appreciate the time and effort that went into this revised manuscript. There are a few issues that still need to be addressed:

MAJOR

1. Please clarify this statement on page 6: "Patients scored 4-9.9, 10-14.9 and 15-20 were regarded as having low, medium and higher global scores of QoL[29, 30]". The cut-off scores are based on the Santos paper, not the Puri paper; and the Santos paper has used these scores based on the general (and not HIV-specific) WHOQOL on a sample of psychiatry graduates/residents. Please justify again the use of the cut-offs either by (a) suggesting that the Puri paper, and hopefully other papers, have adequately justified the use of these scores in spite of the contentious origin of the cutoffs, and discussing it in text either in the methods or discussion; (b) identifying other validated cut-off scores; or (c) using sample-specific cut-off scores of high/medium/low based on quartiles or tertiles or even a medium split and discussing this in text. Given this is the crux of the manuscript, this needs to be addressed before the manuscript can proceed.

MINOR

2. Please also clarify this statement on page 8: "We have approached 311 patients, but data of 240 was included in the analysis giving a response rate of 77.2%". (a) Please comment on how the study is adequately powered in spite of only 240 participants results were still found to be significant; and (b) Please comment on the reasons for non-participation/decline participation.

3. Please acknowledge in the discussion section the limitations of using the subjective self-reported MMAPS-8 vs. more objective measures like pill counts.

4. Please include in the methods that the data was collected via an interviewer-administered questionnaire and justify why it was not collected participant-completed self-reports; please also comment on this potential effect of social desirability bias (especially in the context of HIV/AIDS) on the discussion.

5. Please also comment on page 8 that the demographic distribution of participants approximate that of the sampling frame to allay any issues of biased sampling. 

==============================

Please submit your revised manuscript by Jul 25 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Haikel A. Lim, MD, MSc

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

I appreciate the time and effort that went into this revised manuscript. There are a few issues that still need to be addressed:

MAJOR

1. Please clarify this statement on page 6: "Patients scored 4-9.9, 10-14.9 and 15-20 were regarded as having low, medium and higher global scores of QoL[29, 30]". The cut-off scores are based on the Santos paper, not the Puri paper; and the Santos paper has used these scores based on the general (and not HIV-specific) WHOQOL on a sample of psychiatry graduates/residents. Please justify again the use of the cut-offs either by (a) suggesting that the Puri paper, and hopefully other papers, have adequately justified the use of these scores in spite of the contentious origin of the cutoffs, and discussing it in text either in the methods or discussion; (b) identifying other validated cut-off scores; or (c) using sample-specific cut-off scores of high/medium/low based on quartiles or tertiles or even a medium split and discussing this in text. Given this is the crux of the manuscript, this needs to be addressed before the manuscript can proceed.

MINOR

2. Please also clarify this statement on page 8: "We have approached 311 patients, but data of 240 was included in the analysis giving a response rate of 77.2%". (a) Please comment on how the study is adequately powered in spite of only 240 participants results were still found to be significant; and (b) Please comment on the reasons for non-participation/decline participation.

3. Please acknowledge in the discussion section the limitations of using the subjective self-reported MMAPS-8 vs. more objective measures like pill counts.

4. Please include in the methods that the data was collected via an interviewer-administered questionnaire and justify why it was not collected participant-completed self-reports; please also comment on this potential effect of social desirability bias (especially in the context of HIV/AIDS) on the discussion.

5. Please also comment on page 8 that the demographic distribution of participants approximate that of the sampling frame to allay any issues of biased sampling.

[Note: HTML markup is below. Please do not edit.]

[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.

Health related quality of life of people receiving highly active antiretroviral therapy in Southwest Ethiopia

PONE-D-20-05500R2

Dear Dr. Kefale,

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,

Haikel A. Lim, MD, MSc

Guest Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for your revised manuscript. I am pleased to convey that this manuscript is ready for publication in PLOS ONE. Thank you once again for your submission and professionalism throughout the review process. I wish you the best of luck in your future research endeavours.

Reviewers' comments: