PONE-D-19-31896

Levels and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

PLOS ONE

Dear Dr Ajayi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The reviewers note that this paper reports on an important outcome namely postpartum ART adherence. They note some changes that would strengthen the paper. Please respond to these comments and revise accordingly especially regarding how you defined adherence and how the adherence data was analysed and also address the issue of selection bias.

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Tanya Doherty, PhD

Academic Editor

PLOS 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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

Reviewer #2: No

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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: Summary:

This is a very well written paper and easy to read and understand. It presents an important long-standing issue of attempting to understand the reasons behind suboptimal adherence to antiretroviral therapy (ART) among HIV-positive postnatal women. They find that in the context of a community of the Eastern Cape province of South Africa, three factors are associated with ART adherence during the postnatal period. Young maternal age and alcohol use are associated with poor adherence while knowledge of partner’s HIV status is associated with better adherence. These associations are commonly observed in the rest of the country and other parts of Sub-Saharan Africa. However, the authors were mostly interested in how infant feeding practices influence adherence and they did not find a relationship between ART adherence and infant feeding practices.

Their results probably reflect that even though certain factors are commonly associated with ART adherence and should be addressed with confidence at a population level, the outcome related to the hypothesis behind exploring the influence of infant feeding practices on ART adherence could be masked by the local community’s societal and cultural influences. Future work incorporating perceptions around breastfeeding and HIV infection would be useful.

Although it is a brilliant study, the authors may consider looking into a few suggestions which could make the manuscript stronger. The suggestions are not major but do require the authors’ attention.

Minor Essential Revisions:

1. ABSTRACT – probably mention in a short sentence what method was used to measure adherence.

2. ABSTRACT: Be careful how you interpret results about feeding. There is no indication of statistical significance and the confidence intervals fully overlap a statistic of no significant (OR=0). Therefore, I would recommend you clearly state that there was not relationship between ART adherence and feeding rather than saying feeding ‘tended to reduce the odds of adherence’.

3. STATISTICAL METHODS AND RESULTS:

a. The way you measured adherence appears to be a strong and robust method but however the way you present the results has masked this robust approach. Your method of measuring adherence appears to report an ordered outcome variable with scores ranging from ‘0’ through to ‘6’. An important question is whether scoring a 1 reflects better adherence challenges compared to scoring a 6, on average? If this is true, then your outcome should be ordered from perfect adherence (score=0) to poorest/worst (score=6). It would make sense to have four ordered groups with adherences scores of 0, 1-2, 3-4 and 5-6. You would then check if the ordered logit model fits your data better than your current logistic regression model with a binary outcome (score 0 versus 1-6). You might need to include a supplementary file explaining how you decided the choose the final approach.

b. You need to include a distribution of the adherence scale results for the overall sample, probably in the form of a graph, in the main body of the results section. You mention that ~64% of participants adhered (abstract and discussion), but the reader does not see this clearly from the results section! Did 64% get an adherence score of 0? It is important for the reader to see what proportion of the sample fell into the different scores of the adherence scale 0, 1, 2, 3, 4, 5, 6 or stepwise groups 0, 1-2, 3-4, 5-6. This will also help the reader to understand why you chose a binary outcome over an ordinal outcome or vice-versa. Please add a paragraph describing the main outcome variable in the results section.

c. Under 'Postpartum Adherence to ART' paragraph, you mention that adherence was also lowest among 'students (43.2%)'. Where is this outcome in Table 2?

d. It will be useful to mention what statistic was done to get the p-value reported in Table 2. Yoy may add a table legend with this information.

4. DISCUSSION: In the paragraph which talks about feeding practices, consider discussing the reasons why this dataset did not reflect your hypotheses around feeding and ART adherence? Have you considered the possibility of socio-cultural perceptions around breastfeeding and the stigma associated with HIV if a woman does not breastfeed, in certain settings. If this is true, then breastfeeding will likely be more uniform across the community thus not be a good predictor of adherence. South Africa is largely a breastfeeding country and many rural communities practice breastfeeding religiously.

5. DISCUSSION: You mention that ‘young people are more likely to use alcohol ….’. This statement requires a qualification either from an external reference or from your dataset. Does your data show an association between young age and alcohol use? Otherwise I would not recommend the statement.

6. CONCLUSION: This study has re-iterated associations which have been reported in different contexts within and outside South Africa. Hence emphasis is needed on this and that it is time to focus on designing or strengthening interventions which deal with the risk of young maternal age and alcohol.

Reviewer #2: The study documents a cross sectional analysis of adherence to ARVs and determinants thereof among postpartum mothers with HIV who delivered at a hospital in the Eastern Cape, South Africa. Data collection takes place 18-24 months postpartum and this study appears to be one part of a larger study/ies based on the cohort “The East London Prospective Cohort Study after 18-24 months post-delivery”, although how this analysis fits in with this cohort and any other studies, if at all, is unclear

There are no line numbers, which makes it difficult to be clear about the recommended edits.

Overall: The study needs to be published as the information is useful to health practitioners and policy makers, and will be of interest to researchers. However the quality of the writing needs to be strengthened for publication in PLoS One

Abstract: Give a brief definition of adherence vs perfect adherence – see my point fi Introduction and be consistent throughout

Introduction

1. Please give a succinct account of what perfect adherence involves – daily medications at a specific time – or what – or is there a variation

2. Para 2, 3 and 4: Please can you attempt to rewrite with a more crisp style. Avoid words like “huge”. Also give dates for your statistics

3. Para5: “The Eastern Cape is a resource constrained… “- please correct

Methods

Design and setting

1. Please clarify how this analysis relates to the electronic database – is the database routine surveillance, or research driven. Don’t just refer to other literature.

2. 18-24 months is quite a long time – in the methods and in the results please specify how many months or weeks post delivery the participants were, and if a range – do a bivariate analysis on adherence and if this is significant, include in the MV analysis

Participants

3. Please clarify whether all women in the database were contacted to participate or a sub-sample. If a sub-sample – how were they selected?. If not able to be contacted, what are the characteristics of those who could not be contacted. Please address the question of selection bias thoroughly.

4. There is no sample size calculation – please include or explain why not

Measures

5. Rather than describing the questions, please include them verbatim. Also, I counted only 5 question descriptions .

6. Have the questions been validated against other measure of adherence that are not self-report or are they ‘de novo’– please give details and explanations

Statistical analysis

7. The first 2 sentences fit better into the results. Also include characteristics of those not included in the 509 as well as the 10/509 who did not answer the adherence questions – and give reasons why they didn’t

Para 2

8. Clarify the outcome – “perfect adherence”

9. Typo “A 95% confidence intervals..” – please correct

Results

1. Para 1“Receives” s/b received

2. Please add HIV duration and categories of months/years duration of HIV infection eg. 1.5-2yrs, 2-5 yrs, >5 - or some other meaningful division and include in the Tables , and comment on the result in the discussion. The same for months postpartum

3. Only keep this text if Table 1 is removed. Otherwise it is just a repeat

4. Postpartum adherence: Specify that you mean the overall perfect adherence rate in sentence 1 and thereafter wherever this is the case. Or define adherence earlier in the text to mean perfect and the be consistent throughout the paper only using the word adherence

5. Multivariable findings: Change to Multivariable analyses

6. Remove the word “at least” as it is inaccurate, and cite the 95% CI

Tables

1. Table 1 is unnecessary as the information can be incorporated as a column with n (%) in

2. Table 2: It would strengthen the paper if you divide suboptimal adherence into at least 2 categories – based on the score. The ORs can compare perfect to suboptimal adherence overall, but this additional information is worth informing the reader

3. Add footnotes to Table 3 to explain the *, **, ***

Discussion

1. Para 1 last sentence doesn’t make sense if you include “likely”. Please be specific

2. Para 2.Explain why you assumed breast feeding will influence adherence – perhaps in the introduction and refer back to that with clear reasoning

3. Par 3: Within this paragraph, you give details regarding decline – why not give these in Para1 and link these ideas

4. Study limitations: Replace sentence 1 with “This study has some limitations”

References:

1. Reference 17 is confusing – last author JJBid? no journal stated

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Reviewer #1: No

Reviewer #2: Yes: Deborah Constant

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Levels and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

PONE-D-19-31896R1

Dear Dr. Ajayi,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Tanya Doherty, PhD

Academic Editor

PLOS ONE

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: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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: (No Response)

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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 Response)

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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: All my comments have been addressed satisfactorily. The authors have also included additional discussion points which I suggested.

Reviewer #2: (No Response)

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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