Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysis

Feleke Hailemichael Astawesegn; Haider Mannan; Virginia Stulz; Elizabeth Conroy

doi:10.1371/journal.pone.0300606

Peer Review History

Original SubmissionFebruary 27, 2023
25 Jul 2023 Decision Letter - Felix Apiribu, Editor PONE-D-23-04697Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysisPLOS ONE Dear Dr. Astawesegn, 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 8th August 2023. 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. 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If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments (if provided): The author should do the revisions and submit for final decision. [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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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: Yes Reviewer #3: 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 Reviewer #3: 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 paper is well written and addresses an important question that must be addressed to reach HIV epidemic control goals for countries in East Africa. The paper would benefit from a time-stratified analysis, differentiating between HIV service delivery approaches before and after the World Health Organization's "Treat All" guidelines in 2016. Access to HIV testing and treatment dramatically advanced with this guidance, with many women receiving HIV diagnosis and treatment prior to pregnancy which is known to be superior to diagnosis and initiation of treatment during pregnancy from a PMTCT perspective. As presented, the analysis compiles findings from studies that were conducted in dramatically different HIV service delivery contexts and may not present the most relevant findings for programs. Reviewer #2: The manuscript is well written with minor corrections inserted in the attached. I would be willing to review the revised manuscript,although I don't think it is very necessary given the fact the authors have done a very commendable research work. Reviewer #3: I appreciate the authors contributions for this well written manuscript of public health importance. Authors should provide the confidence intervals of the Adjusted Odd Ratios (AOR). Addressing the strengths and the limitations of the manuscript is commendable. Conclusively, manuscript respects scientific norms for publication. ****** 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 Reviewer #3: Yes: Professor Halle-Ekane Gregory (MD;FWACS) ******** [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. Attachments Attachment Submitted filename: PONE-D-23-04697_BN_reviewers comments_15thJuly2023.pdf https://doi.org/10.1371/journal.pone.0300606.r001
Revision 1
6 Aug 2023 Author Response Date: 06/08/2023 Title: Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysis Dear Editor and Reviewers: We really thank you for your valuable comments/suggestions for the betterment of our manuscript. Your concerns and suggestions are addressed in the revised manuscript and below we have tried to clarify some of the points raised by the reviewers. Reviewer # 1 1. The paper would benefit from a time-stratified analysis, differentiating between HIV service delivery approaches before and after the World Health Organization's "Treat All" guidelines in 2016. Access to HIV testing and treatment dramatically advanced with this guidance, with many women receiving HIV diagnosis and treatment before pregnancy which is known to be superior to diagnosis and initiation of treatment during pregnancy from a PMTCT perspective. As presented, the analysis compiles findings from studies that were conducted in dramatically different HIV service delivery contexts and may not present the most relevant findings for programs. Author response: As you mentioned, there has been a significant shift in the HIV guidelines, such as moving away from considering WHO stage or CD4 count levels to adopting a test and treat approach for the general population in 2016`. However, when it comes to PMTCT, the approach has evolved differently due to its specific goal of preventing vertical transmission. Over the last two decades, WHO has developed various PMTCT guidelines/approaches, such as option A, option B and option B+. Option B+ involves a test and treat approach for HIV-positive pregnant women only with the primary objective of preventing vertical transmission from mother to child and has been in effect since 2012 (Malawi was the first country to implement this in East Africa). Therefore, given the focus of this review on understanding the current status of preventing mother-to-child HIV transmission, articles published after the implementation of Option B+ (since 2012) were included in this review to gather relevant information. Reviewer # 2 2. To my understanding Ethiopia, Mozambique, Zimbabwe, etc are not part of East Africa. I suggest that authors should review or justify the inclusion of these countries. Author response: Regarding the country's classification, there are different classifications of East African countries. In this study, we selected the United Nations Statistical Division and World Health Organization classification of East Africa region as mostly health-related reports and studies considered this classification. We have cited the following reference to indicate the list of East African countries in the manuscript method section (see page 5 lines 128-129). � United Nations Department of Economic and social affairs statistical division. Standard country or area codes for statistical use 2020 [Available from: https://unstats.un.org/unsd/methodology/m49/ � United Nation. World Population Review 2020 [Available from: https://worldpopulationreview.com/country-rankings/east-african-countries Furthermore, recently published studies (including those published by Plos One) using the same countries under East Africa are cited below for the reviewer's consideration: 1. Tesema GA, Tessema ZT. Pooled prevalence and associated factors of health facility delivery in East Africa: mixed-effect logistic regression analysis. PLoS One. 2021 Apr 23;16(4):e0250447. 2. Raru TB, Ayana GM, Zakaria HF, Merga BT. Association of higher educational attainment on antenatal care utilization among pregnant women in East Africa using Demographic and Health Surveys (DHS) from 2010 to 2018: a multilevel analysis. International journal of women's health. 2022 Feb 1:67-77. 3. From the review findings, the authors can suggest specific strategies/implemented target interventions. Author response: Thank you so much. We have included specific strategies/implemented target interventions as part of the discussion and conclusion ( see page 30 lines 537-541) 4. Was the protocol of this systematic review registered? Authors should provide information. Author response: We were unable to register the protocol because of the time limitations we encountered. During that time, we encountered difficulty in registering a protocol on platforms such as PROSPERO, due to the vast amount of reviews related to COVID-19 that had overloaded them. 5. Authors should clarify the meta-analyses mentioned here in relation to the following statement: "...it was not feasible to conduct a meta-analysis to assess the effect of each factor." Author response: Thank you so much. To clarify this, a meta-analysis was done to estimate PMTCT services uptake in percentage, as we have indicated under the method section (page 7 lines 198-199). The result of the meta-analysis for the service uptake has been presented on page 14. Whereas, for the determinants or factors associated with PMTCT service uptake, we did not conduct a meta-analysis because of wide variations in the measurement and classification of the variables between studies (see pages 7 line number 191-194). The result of narrative synthesis for the factor has been presented on pages 15-26 6. General comment: In comparison with previous systematic reviews on the same topic, what are new findings that this review has found different from those that have filled the existing knowledge gap? Author response: Unlike other reviews, this review holistically addressed the uptake and determinants of key PMTCT services cascade such as (i) maternal HIV testing among pregnant/postpartum women, (ii) ART initiation among HIV-infected pregnant/postpartum women, (iii) initiation of ARV prophylaxis for HIV exposed infants (HEIs), and (iv) early infant diagnosis (EID)/HIV test at six weeks of age/ in East Africa. It enables readers to compare uptake and determinants across the cascade. Most previous systematic reviews included only quantitative studies, whereas this review included studies that employed mixed methods (quantitative and qualitative). after the implementation of option B+. Most previous studies done after the implementation of option b+ were focused on determinants of ART adherence, however, this review focuses on determinants of PMTCT cascade uptake 7. Can authors justify, the reasons for not searching for grey literature, and if it has affected their review findings? Author response: To focus on peer-reviewed and published articles. 8. What about limited number of HCWs?? Author response: We have provided suggestions to improve the number of HCWs under the conclusion section ( page 30, lines 540-541) Reviewer #3 9. Authors should provide the confidence intervals of the Adjusted Odd Ratios (AOR). Author response: Thank you, we have addressed this omission in the revised manuscript table 2 (pages 17-21). We appreciate the editor and reviewers for the comments and time taken to read our manuscript. And hope that we have addressed the reviewers’ comments and associated changes in the manuscript to your satisfaction. Thank you. Feleke Hailemichael Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0300606.r002
2 Feb 2024 Decision Letter - Hamufare Dumisani Dumisani Mugauri, Editor PONE-D-23-04697R1Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysisPLOS ONE Dear Dr. Astawesegn, 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 attend to all the outstanding comments raised by the reviewers Please submit your revised manuscript by Mar 18 2024 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, Hamufare Dumisani Dumisani Mugauri, Ph.D. Public Health 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 #3: All comments have been addressed Reviewer #4: 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 #3: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: Yes Reviewer #4: 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 #3: Yes Reviewer #4: Yes ****** 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 #3: Yes Reviewer #4: 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 #3: I have no additional comments for the authors. Furthermore, the comments of the other reviewers, responses, and the modifications made by the authors will improve on the quality of the manuscript. Thank you Reviewer #4: This paper is a systematic review which can provide insights on uptake of PMTCT in the East Africa; indeed the findings may be useful to move forward elimination of MTCT,assuming validity of the conclusion and recommendations. The key innovation is the mixed method both quantitave and qualitative for this systematic review. RESULTS The high variability of the studies included in this meta-analysis makes it difficult to summarize the results and recommendations.Undoubtedly the work was exhaustive, however: despite the detailed description of the objective of the studies considered for the quantitative pole ( column 2 table 1), 1/the main measurement(s) for each of the studies does not appear in Table 1. Several selected studies focus on on antenatal screening, antenatal monitoring and early diagnosis; proportionally fewer studies target antiretroviral treatment during pregnancy or afterward. 2/Classifying the studies in Table 1 according to the target of the PMTCT cascade could be recommended? if possible DISCUSSION AND STUDY LIMITATIONS Within the limits of the study, in addition to those cited, the authors could mention the failure to take into account in their cascade the time of final diagnosis at 18 months of children exposed to HIV;Because, it is the central indicator for the elimination of PMTCT as well as ithey could mention not having taken into account the questions of adherence to antiretroviral treatment of pregnant/lactating women and the retention of mother babies couples in follow-up up to 18 -24 months ( the end of PMTCT CASCADE) In the conclusion and recommendations line 540 541, while mentioning expert mothers, authors should reinforce their references with the experience of mothers 2 mothers. (as this is not coming from the findings of their review) REFERENCES have problem with reference 122 which describes PMTCT in a specific context of key population, here sex workers....which are quite different in profile than general population of pregnant women .... ****** 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 #3: Yes: Professor Halle-ekane Gregory (MD, FWACS) Reviewer #4: Yes: ANNE ESTHER NJOM NLEND ******** [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.0300606.r003
Revision 2
24 Feb 2024 Author Response Date: 15/02/2024 Title: Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysis Dear Editor and Reviewers: We really thank you for your valuable comments/suggestions for the improvement of our manuscript. Your concerns and suggestions are addressed in the revised manuscript and below we have tried to clarify some of the points raised by the reviewers. Reviewers comment Reviewers: The high variability of the studies included in this meta-analysis makes it difficult to summarize the results and recommendations. Undoubtedly the work was exhaustive, however: despite the detailed description of the objective of the studies considered for the quantitative pole (column 2 Table 1), 1/the main measurement(s) for each of the studies does not appear in Table 1. Several selected studies focus on antenatal screening, antenatal monitoring, and early diagnosis; proportionally fewer studies target antiretroviral treatment during pregnancy or afterwards. 2/Classifying the studies in Table 1 according to the target of the PMTCT cascade could be recommended. if possible Authors: Thank you for your comment. I have included targeted PMTCT cascades in Table 1 column 7 with footnote description. Reviewers: Within the limits of the study, in addition to those cited, the authors could mention the failure to take into account in their cascade the time of final diagnosis at 18 months of children exposed to HIV; Because it is the central indicator for the elimination of PMTCT as well as they could mention not having taken into account the questions of adherence to antiretroviral treatment of pregnant/lactating women and the retention of mother babies couples in follow-up up to 18 -24 months ( the end of PMTCT CASCADE) Authors: We appreciate the reviewer's concern. Of course, in places where there is no virological testing, babies typically must wait until they are 18-24 months old to undergo an antigen-antibody test. This is because it's expected that maternal antigen will clear out of the infant's blood by 18-24 months, allowing for accurate antigen tests. However, this review focused on the recommended "early" infant diagnosis, which involves testing HIV-exposed infants within 6 weeks of birth. Early infant diagnosis employs a virological test using DNA-PCR to directly detect HIV. This suggestion is advised to prevent infant deaths, as infants with HIV have a high likelihood of death because of the disease before reaching the age of two. It is advised for countries to establish virological testing using HIV-DNA (PCR) and/or HIV-RNA at least at central or tertiary levels to enable early HIV testing for infants. Therefore, the study, as outlined in the methods section, aims to examine the uptake and determinants of "early infant diagnosis”, involving virological tests before 6 weeks. Reviewers: In the conclusion and recommendations line 540 541, while mentioning expert mothers, authors should reinforce their references with the experience of mothers 2 mothers. (As this is not coming from the findings of their review). Response: As you mentioned, involving expert mothers while dealing with one mother to another was not the finding of the review, we rather recommended involving expert mothers as a solution for the staff shortage we identified in this review. Expert mothers (EMs) are mothers living with HIV who have personal experience with PMTCT programs, which they can draw upon to support other women and their families. Previous studies showed that the involvement of expert mothers in formal health systems in low-resource settings was found to be important for overcoming workload through task sharing. They possess the ability to undertake various tasks within facilities and communities aimed at assisting HIV-positive women and their families. EMs frequently serve as auxiliary staff for services facing staffing shortages. Their responsibilities may include administering routine HIV tests typically conducted by healthcare workers (HCWs), offering pre-and post-HIV test counselling, delivering psychosocial support and guidance on treatment adherence, conducting home visits to assess client well-being, sending reminders for clinic appointments, and tracking patients who have been lost to follow up from PMTCT services. Reviewers: have a problem with reference 122 which describes PMTCT in a specific context of a key population, here sex workers.... which are quite different in profile than general population of pregnant women .... Response: The point is appreciated, and the reference has been removed. We appreciate the editor and reviewers for the comments and time taken to read our manuscript. And hope that we have addressed the reviewers’ comments and associated changes in the manuscript to your satisfaction. Thank you. Feleke Hailemichael Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0300606.r004
1 Mar 2024 Decision Letter - Hamufare Dumisani Dumisani Mugauri, Editor Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysis PONE-D-23-04697R2 Dear Dr. Feleke, 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, Hamufare Dumisani Dumisani Mugauri, Ph.D. Public Health Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0300606.r005

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