Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial

Lynda Stranix-Chibanda; Camlin Tierney; Mauricio Pinilla; Kathleen George; Jim Aizire; Godwin Chipoka; Macpherson Mallewa; Megeshinee Naidoo; Teacler Nematadzira; Bangani Kusakara; Avy Violari; Tapiwa Mbengeranwa; Boniface Njau; Lee Fairlie; Gerard Theron; Mwangelwa Mubiana-Mbewe; Sandhya Khadse; Renee Browning; Mary Glenn Fowler; George K. Siberry; for the PROMISE Study Team

doi:10.1371/journal.pone.0255250

Peer Review History

Original SubmissionMarch 3, 2021
9 Apr 2021 Decision Letter - Giuseppe Vittorio De Socio, Editor PONE-D-21-06961 Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial PLOS ONE Dear Dr. Stranix-Chibanda, 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. You will see that the Referees found your work of some interest. However, they also raised major criticisms. Please respond to all the comments by Reviewers 1 and 2. Please submit your revised manuscript by May 15 2021. 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'. 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We will update your Data Availability statement on your behalf to reflect the information you provide. 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: No 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: Abstract - report the exact p-value instead of p-value≥0.16 in line 65 and p-value≥0.09 in line 67 and anywhere else in the manuscript, unless p-value is less than 0.001 or greater than 0.999. Statistical methods - t-tests to compare z-scores doesn't seem appropriate here; why not conduct an analysis of covariance (ANCOVA) by fitting a linear regression model of the post-randomisation z-scores adjusting for baseline/pre-randomisation z-scores and with treatment group-time interaction to estimate how the z-scores differ between groups at the various post-intervention times when they were measured. A likelihood ratio p-value for the treatment-time interaction would assess evidence for whether the treatments differ at the various time points - this would be a statistically more efficient way to analyse these data. Results - rather than presenting means and confidence intervals, I think table 2 should present means and SEs for each treatment group, followed by the difference, confidence intervals and p-values, for each outcome and time. - actual p-values should be reported all through unless less than 0.001 or greater than 0.999; for example for p≥0.14 in line 323 and p≤0.03 in line 329 Reviewer #2: The article is generally well written with impressive design and study size. The article is generally well analyzed and presented. Except some few sentences I generally agree with the interpretations and summaries. The conclusion in the abstract is emphasizing stunting and underweight “differences”. Based on the data you present, there seems to be no difference at week 0, week 10, week 74 and week 104 (and no clinically relevant difference at week 26). I highly doubt the 0.9% “difference” at 26 weeks which is not seen earlier or later is causally related to the intervention/drugs. Rather, I find it more probable to assume that this is due to either slight measurement inaccuracies or stochastic effects in timing of growth (as growth velocity is not constant). Thus, I suggest the conclusion in the abstract is modified, e.g. as following: “In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head-circumference with no clinically relevant differences between the groups. “ Similarly, with so comparable mean WAZ-measures between the groups, I am also skeptical to the interpretation of difference for underweight. This could be e.g. a threshold effect. If you check two additional thresholds (e.g. -1 and -3) and find similar differences, I would be a little less skeptical to the validity of these differences. As there are multiple comparisons and the study have considerable power and size, you could consider using a p<0.01 significance threshold. More importantly, I would recommend that you emphasize clinically relevant differences rather than statistically significant differences. Thus, the subsequent sentences in the conclusion of the abstract should be aligned with the manuscript, and I would slightly modified the results section accordingly. I think the first sentence of the discussion and the conclusion in the main manuscript is more balanced. Except these essential changes, I find the article excellent and well worth publishing. ****** 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:** Lars T. Fadnes [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. https://doi.org/10.1371/journal.pone.0255250.r001
Revision 1
11 May 2021 Author Response REVIEWER #1: R1.1 - Abstract - report the exact p-value instead of p-value≥0.16 in line 65 and p-value≥0.09 in line 67 and anywhere else in the manuscript, unless p-value is less than 0.001 or greater than 0.999. Thank you for the comment. We have revised the Abstract [see lines 66 and 68] to show that the several p-values presented there were all >=0.16 and >=0.09, respectively, and trust that this adequately addresses the concern raised. R1.2 - Statistical methods - t-tests to compare z-scores doesn't seem appropriate here; why not conduct an analysis of covariance (ANCOVA) by fitting a linear regression model of the post-randomisation z-scores adjusting for baseline/pre-randomisation z-scores and with treatment group-time interaction to estimate how the z-scores differ between groups at the various post-intervention times when they were measured. A likelihood ratio p-value for the treatment-time interaction would assess evidence for whether the treatments differ at the various time points - this would be a statistically more efficient way to analyse these data. We understand the approach suggested by Reviewer 1, however, the protocol-specified primary objective was to conduct a cross sectional comparison at postpartum Week 26, with the primary outcome measure of LAZ. Other timepoints and measures were secondary. After discussion by the writing team, we decided to clarify the statistical analysis approach in the revised text [see Statistical Methods lines 221-225 and Abstract line 57] and believe that the explanation is now clear. R1.3 - Results - rather than presenting means and confidence intervals, I think table 2 should present means and SEs for each treatment group, followed by the difference, confidence intervals and p-values, for each outcome and time. Table 2 has been adjusted in line with Reviewer 1’s comment and week 0 infant anthropometric measures were moved to Table 1 [see lines 300-309 in the revised manuscript]. Please note that we took the opportunity to correct an erroneous percentage for stunting in Table 2. The text preceding the table, table title, and footnote were updated accordingly. Table 1 was updated thus: addition of week 0 LAZ, WAZ, and HCAZ under infant characteristics (including % z score < -2); removal of rows for “N” for maternal characteristics (since they are redundant given the column headers and # missing); addition of 10%-90% for infant characteristics (to be consistent with the descriptive statistics presented for mothers); footnote updated accordingly [see lines 271-279]. R1.4 - Results - actual p-values should be reported all through unless less than 0.001 or greater than 0.999; for example for p≥0.14 in line 323 and p≤0.03 in line 329 We have attempted to address this concern by clarifying that we present several p-values in the examples mentioned where no actual p-value is shown. Please see the inserted text in the revised manuscript [for example in line 333]. REVIEWER #2: R2.0 - The article is generally well written with impressive design and study size. The article is generally well analyzed and presented. Except some few sentences I generally agree with the interpretations and summaries. Thank you for the comment. R2.1 - The conclusion in the abstract is emphasizing stunting and underweight “differences”. Based on the data you present, there seems to be no difference at week 0, week 10, week 74 and week 104 (and no clinically relevant difference at week 26). I highly doubt the 0.9% “difference” at 26 weeks which is not seen earlier or later is causally related to the intervention/drugs. Rather, I find it more probable to assume that this is due to either slight measurement inaccuracies or stochastic effects in timing of growth (as growth velocity is not constant). Thus, I suggest the conclusion in the abstract is modified, e.g. as following: “In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head-circumference with no clinically relevant differences between the groups. “ Thank you for the insight and the suggested revision which was considered by the writing team. We opted to use the sentence you provided for the Conclusion in the Abstract [see lines 71-82 in the revised manuscript]. R2.2A - Similarly, with so comparable mean WAZ-measures between the groups, I am also skeptical to the interpretation of difference for underweight. This could be e.g. a threshold effect. If you check two additional thresholds (e.g. -1 and -3) and find similar differences, I would be a little less skeptical to the validity of these differences. We hope the adjusted interpretation presented in the revised manuscript likely addresses this concern. To explain the -2 SD threshold selection, that is the standard clinical definition for stunting and underweight based on World Health Organisation definitions and is not driven by study data. Thus, we made minor clarifications to the Methods and inserted new reference #21 to illustrate the basis for that threshold in the revised manuscript [see lines 237—239]. However, we did carry out a sensitivity analysis around -2, with thresholds of -1.9 and -2.1 to address potential random noise right around this measurement that could result in disproportionate assignments to one category. Results were very similar, and we determined there was no need to include them in the manuscript. R2.2B - As there are multiple comparisons and the study have considerable power and size, you could consider using a p<0.01 significance threshold. Indeed, this study does have considerable size. The 0.05 significance level was pre-specified in our analysis plan. R2.2C - More importantly, I would recommend that you emphasize clinically relevant differences rather than statistically significant differences. Thus, the subsequent sentences in the conclusion of the abstract should be aligned with the manuscript, and I would slightly modified the results section accordingly. We agree with Reviewer 2’s helpful guidance. Accordingly, we revised the Conclusions in the Abstract [see lines 71-82] and removed the term ‘significant’ from several sentences in the Results section [see lines 314-346] to remove any misrepresentation of clinical relevance. We do include p-values in Table 2, as suggested by Reviewer 1 (comment R1.3), but they are not emphasized heavily in the text. R2.2D - I think the first sentence of the discussion and the conclusion in the main manuscript is more balanced. Except these essential changes, I find the article excellent and well worth publishing. Thank you for the insightful comments and suggestions which we have taken on board and used to strengthen the manuscript we now resubmit. EDITOR'S COMMENTS These have been attended to within the cover letter, as instructed. There are no supplemental files for this submission -- the protocol and COSORT checklist were submitted as supplemental files after the initial package was uploaded following guidance. Attachments Attachment Submitted filename: Response to Reviewers_PONE-D-21-06961 [R1].pdf https://doi.org/10.1371/journal.pone.0255250.r002
8 Jun 2021 Decision Letter - Giuseppe Vittorio De Socio, Editor PONE-D-21-06961R1 Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial PLOS ONE Dear Dr. Stranix-Chibanda, 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. We invite you to submit a revised version of the manuscript that addresses minor suggestions by Reviewer #1 and #2. Please submit your revised manuscript by 30 June 2021. 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. 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, Giuseppe Vittorio De Socio, MD, PhD Academic 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: (No Response) ******** 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 Response) ****** 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 Response) ****** 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: Please correct the typographical error at the top of page 11 of 24 - you mean Kruskal-Wallis, not Kruskal-Wallace. Reviewer #2: I think the article has improved and that the first response is fine. I do not fully agree with the approaches on question 2.2, but that being said the discussion of that finding and conclusion still look generally fine. I am aware that z-score -2 is a commonly used threshold for stunting and underweight, but e.g. -3 is also a commonly used threshold for severe underweight/stunting. See also the article by Briend et al. on arguments for not only focusing on a single threshold (Briend A, Van den Broeck J, Fadnes LT: Target weight gain for moderately wasted children during supplementation interventions - a population-based approach. Public health nutrition 2011:1-7.) I do not see the option of adding sensitivity analysis for z-score thresholds of -1.9 and -2.1 (which is very close to the original analysis) as good alternatives to what I suggested of a sensitivity analyses with z-score thresholds of -3 and -1. Unless you see similar results with thresholds of -3 and -1, I think the presentation of differences in the results section is not optimal. However, if you show similar trends for sensitivity analyses, you will probably convince me of your presentation/interpretation. For the results section as I consider the confidence intervals for the dichotomous outcomes are relatively wide (stunting/overweight), I suggest sensitivity analysis with thresholds further away from the original analysis (and that these preferable are added as a supplementary table) to guide whether these are threshold effects. If so, that could be mentioned shortly in the results/discussion section. Also a note relating to the p-value threshold, even though p<0.05 was predefined, it is still possible to guide interpretation not only dichotomously but to discuss degree of association (and chance of random associations versus causal inferences). That being said, the study and article is generally very good and well worth publishing. I just think adding a sensitivity analysis which is more different from the original analysis would lift the paper even more. ****** 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: Yes:** Lars Fadnes [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. https://doi.org/10.1371/journal.pone.0255250.r003
Revision 2
30 Jun 2021 Author Response REVIEWER #1: [Revision 1] R1.1 - Please correct the typographical error at the top of page 11 of 24 - you mean Kruskal-Wallis, not Kruskal-Wallace. Thank you for identifying this error which is corrected in line 228 of the marked-up revised manuscript [Revision 2]. REVIEWER #2: [Revision 1] R2.0 - I think the article has improved and that the first response is fine. Noted. [Revision 1] R2.1 - I do not fully agree with the approaches on question 2.2, but that being said the discussion of that finding and conclusion still look generally fine. I am aware that z-score -2 is a commonly used threshold for stunting and underweight, but e.g. -3 is also a commonly used threshold for severe underweight/stunting. See also the article by Briend et al. on arguments for not only focusing on a single threshold (Briend A, Van den Broeck J, Fadnes LT: Target weight gain for moderately wasted children during supplementation interventions - a population-based approach. Public health nutrition 2011:1-7.) I do not see the option of adding sensitivity analysis for z-score thresholds of -1.9 and -2.1 (which is very close to the original analysis) as good alternatives to what I suggested of a sensitivity analyses with z-score thresholds of -3 and -1. Unless you see similar results with thresholds of -3 and -1, I think the presentation of differences in the results section is not optimal. However, if you show similar trends for sensitivity analyses, you will probably convince me of your presentation/interpretation. For the results section as I consider the confidence intervals for the dichotomous outcomes are relatively wide (stunting/overweight), I suggest sensitivity analysis with thresholds further away from the original analysis (and that these preferable are added as a supplementary table) to guide whether these are threshold effects. If so, that could be mentioned shortly in the results/discussion section. The writing team accepted the reviewer’s comment and are grateful for the reference provided. We agree with not focusing on a single threshold for this secondary outcome measure. We conducted additional sensitivity analyses using thresholds further away from the original z-score threshold (-2.0). For length-for-age (LAZ), the thresholds used were -1.0 and -3.0, as suggested. However, the number of infants with weight-for-age (WAZ) below -3.0 was very low (<2%) at all time points, therefore the thresholds used for WAZ were -1.0 and -2.5. The direction of the odds ratio estimate remains consistent across the different thresholds for both LAZ and WAZ. The results of this sensitivity analysis are now mentioned in line 333 of the marked-up revised manuscript [Revision 2]. The sensitivity analysis results are uploaded with this rebuttal letter for review. We have included a table as new Supporting Information for the revised manuscript (caption inserted at the end of the manuscript document), and include figures below illustrating additional thresholds for the LAZ and WAZ comparisons (Figure A and Figure B - uploaded in the separate document Response to Reviewers). [Revision 1] R2.2 - Also a note relating to the p-value threshold, even though p<0.05 was predefined, it is still possible to guide interpretation not only dichotomously but to discuss degree of association (and chance of random associations versus causal inferences). That being said, the study and article is generally very good and well worth publishing. I just think adding a sensitivity analysis which is more different from the original analysis would lift the paper even more. We reviewed the manuscript with this note in mind. In Revision 2, we removed “significant” from the Abstract and Results in lines 64 and 304, and p-values in lines 70 and 325. Upon review, we revised lines 359-360 in the Discussion that appeared to rely too heavily on the p-values. Figure A. Sensitivity of odds ratio estimate to varying length-for-age Z-score (LAZ) binary categorization Figure B. Sensitivity of odds ratio estimate to varying weight-for-age Z-score (WAZ) binary categorization Attachments Attachment Submitted filename: Response to Reviewers [R2].pdf https://doi.org/10.1371/journal.pone.0255250.r004
13 Jul 2021 Decision Letter - Giuseppe Vittorio De Socio, Editor Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial PONE-D-21-06961R2 Dear Dr. Stranix-Chibanda, 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, Giuseppe Vittorio De Socio, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0255250.r005
Formally Accepted
4 Aug 2021 Acceptance Letter - Giuseppe Vittorio De Socio, Editor PONE-D-21-06961R2 Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial Dear Dr. Stranix-Chibanda: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Giuseppe Vittorio De Socio Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0255250.r006

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