PONE-D-23-13490Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptivesPLOS ONE

Dear Dr. Masson,

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“The research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institute of Health under Award Number R01HD096937-01 (PIs: Morrison, Deese and Masson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. LM was supported by the Carnegie Corporation of New York, South African National Research Foundation and Australian National Health and Medical Research Council. The Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial was supported by the combined generous support of the Bill & Melinda Gates Foundation [grant OPP1032115]; the American people through the United States Agency for International Development [grant AID-OAA-A-15-00045] the Swedish International Development Cooperation Agency [grant 2017/762965-0]; the South Africa Medical Research Council; and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.”

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: This is an interesting study finding an alarmingly high prevalence and incidence of STIs among a population highly vulnerable to HIV. I think changes need to be made to the structure and the methodology before it is published. I will gladly review it again more thoroughly once my main concerns have been addressed. These are:

1. I find it unclear what the aim of the analysis is. Is it to estimate STI prevalence and incidence in this population, or is it to explore the possible relationship between type of contraceptive and STI incidence? Please make the aim clear, explicitly with an aim statement at the end of the Introduction and implicitly throughout the narrative of the paper.

2. I would request that a statistician also review the paper. I have a number of concerns:

a. Incidence should be defined

b. The reason for using keplan meier and the benefit of that approach is unclear to me

c. The reason for plotting the age groups separately is also unclear. Is it to test a hypothesis that incidence would differ by age? The age categories seem somewhat arbitrary. How were they decided upon?

General language suggestions:

There are too many accronyms. As a minimum, I suggest referring to the MRU site as the eThekwini site instead, and the SRC as the Tschwane site.

Define wy when first used

I’m not sure this makes sense: ‘seeking effective contraception with no medical contraindications to trial contraceptive methods’

Reviewer #2: Very good piece of research. I have a few minor comments.

In the introduction I would reccomend changing the statements to "can cause shedding" and "can affect fertility" as it is not true in 100 percent of cases. I also reccomend splitting up the long list of reasons why women may be more susceptible to acquiring an sti. The list is long and the references need to match the risk factors presented. Also categories such as "gender inequality" is too broad. It is important to be more specific as to how these risks arise and why they are specific to young women.

There are some formatting issues in the table where the rows are not vertically aligned. And I think each table needs a description of the p-value definition. Particularly table 3 which has a "P-value" column alongside three columns under the heading "p-value". Descriptions in the text or table caption would improve clarity for the reader.

I also think the discussion should mention that the individuals in the cohort are also hiv seronegative and discuss the bias that may arise from this restriction.

Reviewer #3: Review for "Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives"

PONE-D-23-13490

Reviewer: Tim Lucas, University of Leicester, UK

Date: 2023-07-03

Overview

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This paper presents data and analyses of incidence and prevalence of a number of STIs (not including HIV) in South Africa.

I have no expertise in STIs, but have been asked to review this paper as a statistician, so I will keep my comments within that area.

Overall the analyses seem sensible and the paper is well written.

I have a number of fairly minor points that I think could be clarified in the paper.

Minor Comments

---------------

My most pressing concern is the way in which the multiple-testing adjusted p values have been presented (though I would like to thank the authors for taking this issue seriously throughout the analysis).

Given that the procedure asks for all p values to be sorted, and then adjusted according to their rank, can I confirm how this has been conducted.

Has every single p value in the entire paper been put into one long list and ranked?

Or is each table of p values ranked and adjusted separately?

I think either is fine, I would just like it to be clear in the paper.

Furthermore, I think it might help interpretation if both the adjusted and unadjusted p values were presented (though I realise this might not always be easy without making the tables quite complex).

Given that the smallest raw p values are adjusted more than the bigger p values, it could well be case that the variables with the smallest adjusted p values are not the variables with the smallest unadjusted p values.

I think triangulating these two pieces of information would be useful.

The reference given for this procedure (Columb and Sagadai 2006) has a typo in the FDR step-down procedure. In step 2 they say P' = P(m / (m - (m - 1))). However, m - (m - 1) in the denominator is just equal to 1 so there's clearly a mistake. I'm not sure what the correct expression is though. But if you have directly coded up this procedure based on the equations in this paper, you will need to find the right equation and recalculate.

I would appreciate some more information in the paper about what effect the treatment/acquired immunity for these STIs has on subsequent infection and the exact ordering of treatments. Do these diseases confer immunity? You state that the baseline time is immediately before contraceptive method initiation. Were participants treated for existing STIs, and then contraception was initiated afterwards? Or was treatment initiated at the same time as contraception? If treatment was initiated at the same time as contraception this would cause some issues as presumably a course of antibiotics would be protective against reinfection.

Is there any expectation that the implementation of contraception would directly prevent sexual activity due to discomfort or due to directions from the health workers? And importantly, is this effect different across the contraception methods?

A note clarifying the role of herpes in the study would be useful. It is measured at baseline, and then not treated (as there is no treatment) and not measured in follow up. This all makes sense given the very different epidemiology of herpes compared to some of the other diseases, but I found it a bit confusing while reading the paper working out exactly what was happening.

You have tested whether the different methods of contraception yield different incidences. I might have missed it, but some statements about why you are testing this would be useful. As above, I have no expertise in this area, but I wouldn't expect these methods of contraception to alter STI infection rates. So is this just to confirm this fact? Or is there a hypothesis that the contraception methods might alter behaviour in different ways? Or something else.

Figure 2 is quite low resolution and hard to read.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Tim Lucas

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PONE-D-23-13490R1Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptivesPLOS ONE

Dear Dr. Masson,

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 have submitted a copy of the manuscript with tracked changes, but most of the changes you state in the response sheet that you have been made, are not highlighted in the tracked changes file. This makes it difficult to evaluate e.g., final response to Reviewer #2, you state that you have added a paragraph to the Discussion, but it is not pasted into the Response Sheet or highlighted in the manuscript. Please upload a copy of the manuscript with all changes appropriately highlighted.

Reviewer #3 recommends that you present unadjusted and adjusted p-values, but you make no response to this.

PSA testing as a test for semen detection should be made clear in the Methods section - currently it's only made clear in the Discussion.

Please submit your revised manuscript by Dec 03 2023 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Rebecca F. Baggaley

Academic Editor

PLOS ONE

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Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives

PONE-D-23-13490R2

Dear Dr. Masson,

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