PONE-D-22-19444Strengthening Health System’s Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS’Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa.PLOS ONE

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Additional Editor Comments:

Just as observed by the reviewers, the methods is confusing. The authors have to clarify exactly what they will be doing. I suggest the following

Abstract

- present all methods related to the quantitative study first. Present the qualitative methodology afterwards. Please dont mix up the two

- 'The questionnaire study population comprises of 231 healthcare providers and AGYW aged 15-24 years and ABYM aged

15-35 years old.' This is quite confusing because the authors mentioned that they will be interviewing 1100 participants.

Introduction

- the authors should include additional references. Ref 3 has been cited too often.

Methods

- About how many clients test for HIV at the clinics. The authors should specify, since this will influence the number the participants they will be able to recruit

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

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Reviewer #1: No

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have set out to outline the study protocol entitled Strengthening Health System’s Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS’Cap-Linkage). The proposed study is timely and critical in the HIV and AIDS treatment continuum landscape, particularly for South Africa which has the words largest HIV treatment programme. This study seeks to monitor linkages to, and retention in HIV care among adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM) in uMgungundlovu district, KwaZulu-Natal. The study also seeks to study the HIV testing experiences of AGYW and ABYM who have been newly diagnosed with HIV, comparing these experiences across different service delivery models. By doing this, this study will potentially describe the success of different treatment delivery models. My overall impression of the study is that it has been well designed and articulated in the study protocol.

The protocol highlights that there is evidence of adequate literature review that has been consulted in the development of this study, with a clear outline of the research gap that is being addressed. However, there are updated figures that could be used with respect to the 95-95-95 targets with authors quoting 2018 data. I suspect this is from the original protocol developed at the onset of the study.

The study appropriately intends to utilise a mixed methods approach with the purpose of providing evidence that can improve linkages to, and retention in HIV care services for AGYW and ABYM.

The study objectives have been clearly listed and described, and a clear and robust methodology has been provided making it understandable to see how the study objectives will be achieved.

It is difficult to request authors to improve on areas as it would appear that the study is already past the half way point with the investigators committed to these protocols. There is therefore little value in reviewing beyond requesting clarity.

Having said that, perhaps the authors could address and provide clarity in the following areas:

1. The definition of ABYW is not consistent with extent literature, including literature cited in this manuscript. On page 4 second paragraph you refer to adolescents and young people as being between 15-24, including specifically referring to ABYM. To therefore have an expanded definition as reference to your target population is problematic.

2. Your abstract should ideally articulate your primary objective.

3. I would split your objectives into your primary of objective - which is to quantify the linkage and retention rates among HIV positive ABYM & AGYW.

4. Consider just combining stating adolescents and young people (AYP). You can then stratify results by sex.

5. With respect to your section on Setting - why not provide the prevalence of your target population.

6. I think there is a problem with your first stated study question - determining the available service delivery models. Later in the study you have committed to evaluating the three delivery models (facility based, school-based and community based). Does this not render this question redundant?

7. I would strongly encourage the investigators to adopt the language of losses to follow-up (LTFU). We are aware the LTFU might prevent the long-term success of HIV treatment and might delay the achievement of the 95–95-95 objectives. It would have been useful if this study described and analysed of the strategies used to reengage LTFU in HIV care, their implementation and impact. Perhaps beyond the scope of this study but also aligns with the newly published guidelines by WHO (2021). Specifically it states that HIV programmes should implement interventions to trace people who have disengaged from care and provide support for re-engagement. Further, psychosocial interventions should be provided to all adolescents and young adults living with HIV. This study is opportune to evaluate this.

8. Heading: Study Population and recruitment: The penultimate sentence beginning 'This cohort..." needs to be revisited. The word 'collection' may be missing at the end.

9. Given that the study has begun - it may be helpful to add a paragraph describing any deviation from the protocols.

10. The sample size calculation could potentially be problematic. Authors used the LTC rate of 62% without factoring in differences across age cohorts - given that this study is focusing on a particular cohort. Further, as far as I'm aware the LTC rate is drawn from facility based models which I would expect to be higher than school or community based models - where following a positive test the individual will then have to make their way to a clinic. However, it is a conservative estimate give more recent data on a neighboring district.

11. PLOS requires that the data be accessible - either through a data repository or accessible from the PI - this will need to be stated

12. Your listed enablers and barriers appear to be missing a few things which the literature has suggested are important. Many reasons have been given for delayed commencement of ART and these include patient’s choice, prolonged adjustment periods, transport costs due to distance from health facility (be specific about the costs), stigma and fear of disclosure. Other factors associated with delayed ART uptake are staff shortages, long waiting times, fear of drug side effects, and the need to take time off work/school. Furthermore, there are factors that have been associated with delay or lack of linkage to care including lower levels of education, feeling well at diagnosis and alternate healing systems. Not clear that these issues are being analyzed.

13. I would have also included: Baseline clinical characteristics which could have included opportunistic infections, body mass index (BMI), functional status, pregnancy status, any current health complaints, WHO clinical stage and mode of HIV testing (VCT or PICT). Behavioral characteristics such as sero-status of sexual partner, disclosure status, and HIV test history, number of sexual partner/s, condom utilization, and alcohol use. HIV and ART related Knowledge, history of STI. Psychological characteristics could include perceived stigma and psychological distress.

14. With respect to the qualitative work it could have potentially have been enhance by adopting a descriptive phenomenological design. This type of phenomenology places the emphasis on descriptions of personal experiences and delineations of how and what the individual hears, sees, feels, believes, remembers, decide and evaluates. In this particular instance, the search for meaning with regard to the experiences of HIV-positive adults in respect of ART initiation.

15. The authors could provide a justification for sample size, particularly for the qualitative component where it has been stated that 30 participating patients who successfully linked to care, 30 who are not, and 30 who have never tested for HIV will be sampled. It also has not been stipulated whether the proposed sample representative of the target population- this information could be useful. The authors have provided a recruitment plan with a clear inclusion and exclusion criteria, perhaps the authors could provide details on the timelines for their recruitment goal over the 24 months stipulated for data collection.

Finally - wishing the researchers best of luck with this work. I look forward to the results.

Reviewer #2: Overall this is a well written protocol. There are sections a bit repetitive. I have comments around the study design and sample size calculations.

Study design is confusing. For example, the section titled “study design” on page 7, doesn’t mention anything about “clustered” nature of the study. If this is a clustered-design study, then, power/sample size calculations need to account for the design effect which is: 1+ (cluster size-1)*(intra-class correlation coefficient)

In sample-size calculation, there is no information regrading the design effect. In addition, what is the rational for selecting ICC=0.01? selecting such a low ICC indicates almost “no cluster” effect

Study has also a longitudinal aspect. There is no information regarding the “loss-to-follow up”

The investigators randomly mentioned that:

“Primary outcomes will be evaluated using a logistic regression model. A time to event analysis will also be conducted taking the study design into account.” with no further information for the "time to event analysis"

Which outcome(s) will be analysed using a time to event analysis? If there is a time to event data, then survival type of analysis such as Cox regression models should be used but there is no mention in the protocol for such analysis. The investigators only mentioned “logistic regression models” which suits cross-sectional data only. Given the study has clustered-design component, how this will be accounted in logistic regression models?

What are the potential confounders that the investigators are talking about on page 2?

minor comments:

Why the age cut points are for men and women are different? While 15-24 years old

Looking at the Introduction: the vast majority of the background information was referenced using only one reference which is reference #3:

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Reviewer #1: Yes: Gavin George

Reviewer #2: No

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Strengthening Health System’s Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS’Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa.

PONE-D-22-19444R1

Dear Dr. Nicol,

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Kind regards,

Sandra Boatemaa Kushitor, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: