PONE-D-22-26544Prevalence of delayed antiretroviral therapy initiation among people living with HIV: a systematic review and meta-analysisPLOS ONE

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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: 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: 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: Yes

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: Please consider the following comments:

1. The manuscript should be proofread carefully.

2. Line 15: Please delete the working definition for delayed antiretroviral therapy

3. Line 21: Please provide both names of the database and platform (e.g. Pubmed/Medline)

4. Line 23: Why the authors used both approaches for detecting heterogeneity?

5. Line 24: Meta-regression is not an approach for identifying potential sources of heterogeneity

6. Line 29-30 It seems the sex disparity does not reach the significant difference

7. Line 31-32: How about the results of CD4 level in meta-regression? Please also provide the CI for the results.

8. The content of the introduction is a bit biased. Initiation of ART in the setting of an acute, AIDS-associated opportunistic infection does not follow the "the earlier the better" rule. For some opportunistic infections, such as cryptococcal and TB meningitis, immediate ART initiation may increase the risk of serious Concerns regarding immune reconstitution inflammatory syndrome. A short delay before initiating ART may be warranted. For patients with mild to moderate cutaneous Kaposi sarcoma, initiation of ART can not be done with chemotherapy. Drug interactions should be considered when starting ART.

9. Therefore, pooling the numbers of delayed ART initiation may not guide the clinical practice. The justification for the significance of this review is not clear enough.

10. Line 100 The term "systematic review" and "meta-analysis" are used interchangeably.

11. Line 100 Do You mean non-randomized studies? why does this review exclude randomized studies?

12. Line 101 why does this review include minors?

13. Line 129-133 Please provide the statistical details of meta-regression and sensitivity analysis.

14. Figure 1 The authors stated this review complies with PRISMA 2020. However, the PRISMA Flowchart did not fit the updated PRISMA.

15. Table 1 Please provide only the surname of the first authors.

16. Table 1 Please provide the details of participants' characteristics including mean/median age, age range, sex, study setting, etc.

17. Table 1 Ross J et al Please provide the reasons in the footnote why this study did not report the quality score

18. Table 2 P for the difference in subgroups is needed

19. Table 2 What do you mean by male and female subgroups? only including male/female? or the majority proportion?

20. Table 2 mean age or median age? Do included studies report median age?

21. Table 2 mean CD4 or median CD4?

22. Table 3 It seems the authors misunderstand the difference between meta-regression and subgroup analysis. Year of publication, continent, country, country income, study design, sample size, and quality score could not be the covariates of prevalence of delayed ART initiation. Meta-regression usually included individual-level variables in regression models in each study.

23. Result what are the confounding factors set in the NOS?

24. Did the authors search grey literature?

25. Discussion: As I mentioned above, the delayed use of antiretroviral agents highly relies on the type of OI. This info should be mentioned in the discussion. Considerations when initiating ART are complicated.

26. The heterogeneity was high in all models. It should be listed as a limitation

Reviewer #2: General Comment:

This manuscript reported a systematic review studying the prevalence of delayed treatment (ART) to AIDS and its relevant factors. Overall, this paper contributed important knowledge to the literature. To improve the quality of the manuscript, I listed some suggestions below.

Major Comments:

1. Line 100. “No-randomized” is confusing. Did the study only include non-randomized studies?

2. Line 101. Why did the authors only include studies published between January 2015 and August 2022?

3. Line 103-105. I suggest that the authors provide the reason(s) of excluding studies conducted among pregnant women.

4. Line 108-109. The two authors’ (Tao and Xie) reviewing process was not clearly described. For example, what were the “remaining relevant articles”?

5. The clarity of the process of screening titles and abstracts needs to be improved. For example, in Figure 1. “Record screened by title and abstract” appeared twice.

6. Line 153. I suggest that the authors explain the quality scores. For instance, what does the score of 3 mean?

7. The resolution of figure 2 needs to be increased. The current version is difficult to read.

8. The line 22 on page 17. The first rationale mentioned in the sentence – “the possible reason for the age difference is…for longer” – is difficult to understand. Also, the second rationale – “In addition, they usually…for young HIV-infected people” – is not convincing and needs to be rephrased.

9. The line 9-10 on page 19. The second limitation was difficult to understand. Its clarity needs to be improved.

Minor Comments:

1. Line 55. Please name the countries where the observational studies were conducted.

2. Line 73. There is a grammar error. “Such time from…” needs to be revised to “such as time from…”

3. The manuscript will be strengthened, if the transition between the 3rd and 4th paragraphs could be improved.

4. Line 83. The sentence “…global prevalence of delayed initiation for the time from diagnosis to ART initiation…” is difficult to understand. I suggest rephrasing this sentence.

5. Line 145. I suggest deleting the word “subjects”.

6. In the section of subgroup analysis, the authors mentioned “high-income countries”, “upper-middle income countries”, and “lower-middle income countries”. I suggest adding a column in Table 1 to show the category of each country.

7. Page 17. Some interventions mentioned in the discussion section were not clear. For example, what specific interventions were taken to streamline initiation of ART? What was the specific content of the “grassroots prevention and control service model”?

8. In the section of acknowledgements, the authors state that they thank all colleagues working in Xiangya Nursing School. This section will make more sense if the authors could briefly provide 1 or 2 reasons to illustrate why all colleagues need to be acknowledged.

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Reviewer #1: No

Reviewer #2: Yes: Zhao Ni

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Prevalence of delayed antiretroviral therapy initiation among people living with HIV: a systematic review and meta-analysis

PONE-D-22-26544R1

Dear Dr. Wang,

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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Lara Vojnov

Academic Editor

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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

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

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: Yes

Reviewer #2: No

**********

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: I am satisfied with the revisions made to the manuscript. Thank you for your diligent efforts in addressing the concerns and improving the overall quality of the document.

Reviewer #2: The authors addressed my comments. There are still some grammatical errors in the manuscript. For example, "clinical management of these patients beingcomplex." should be revised to "clinical management of these patients is complex."

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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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