PONE-D-19-35399

Provider-initiated HIV testing and TB screening in the era of universal coverage: are the right people being reached? A cohort study in Blantyre, Malawi

PLOS ONE

Dear Dr. Mair,

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 review the feedback and requests from clarification from the two reviewers, and provide a detailed point-by-point response.

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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: Partly

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: Yes

Reviewer #2: Yes

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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: Overall

This manuscript describes a prospective cohort study undertaken in an adult primary care clinic in Blantyre Malawi to evaluate whether clinic attendees were offered PITC and to compare same day HIV testing rates between participants reporting TB symptoms vs those reporting no TB symptoms. From other data, rates of undiagnosed HIV are high among clinic clients reporting TB symptoms, therefore should be prioritized for HIV testing. The investigators relied on self-report of HIV-testing upon exit interview, and only 44% of clinic attendees underwent exit interview.

The main finding of the study was that among participants undergoing exit interview, only 27.6% reported being offered testing, with 21.5% completing PITC and receiving HIV test results. Testing offered was relatively similar among those with and without TB symptoms. The multivariable regression model indicated men, younger adults, and participants who had previously undergone HIV-testing were more likely to complete HIV testing than women, older adults, and those who had not previously been tested for HIV.

Although an important topic- universal HIV testing as well as importance of HIV testing among those with TB symptoms, the paper could be strengthened by a number of additions/clarification:

-The authors do not included data regarding proportion of participants who report TB symptoms (and those without TB symptoms) who were diagnosed with HIV. This is an important data point and could be used to support their hypothesis that clinic goers with TB symptoms are a high yield population to test.

-Only 44% of clinic goers underwent exit interview. I wonder if it is possible to also reconstruct the cascade of testing and testing results utilizing the registers from the clinic over the same time period. Although these registers may not include the results of the TB symptom screen, they would provide an objective snapshot of number of clinic goers offered testing, undergoing testing, and testing results and would be very informative.

-Additionally, it appears clinic attendees with TB symptoms were less likely to undergo exit interview. The authors should clarify how this may have biased their results. Perhaps participants who had TB symptoms did under HIV testing, but they weren’t captured for some reason in the exit interview?

-Is the reason for clinic appt recorded? If so, would also include in the models of testing. Perhaps certain presenting complaints (or even primary diagnosis of the encounter) are related to testing offer, uptake, and diagnosis.

Introduction/Methods

-Suggest clearly stating what the Malawian guidelines are for testing adults in a primary care clinic are.

-Authors mention these visits are for acute care, but my assumption it is for all-comers. Please clarify

Methods

-If possible, briefly describe what the pragmatic RCT will focus on.

-Describe what the Malawian PITC guidelines are.

-Is TB care provided at the clinic, or are patients referred somewhere else. What are the next steps for patients with TB symptoms at the clinic? Perhaps if they are referred somewhere else this could account for the fact that they were difficult to reach for exit interviews

-Be consistent RE: capitalization for Research Assistant.

-Clarify if PITC is to be offered for those with a negative test >90 days, or unknown HIV status (these details aren’t mention- I’m just assuming this is the guideline).

-Investigators mention excluding known PLHIV who were already taking ART, but what about known PLHIV not yet on ART? Were they also excluded? If so, clarify.

Results

-Are reasons for attendance to clinic, or clinic visit diagnosis available? Per above this may influence HIV testing as well.

-Was clinic flow different for patients who reported TB symptoms? Would they have been tested for HIV at another clinic (i.e. during further TB workup?).

-Were reasons test refusal among those offered testing recorded?

-Was time of last reported test recorded? Consider including in model.

Discussion

- Mentions that majority of health centers use symptom-based PITC, as opposed to universal offer. Is this in agreement with Malawi PITC guidelines?

-ROOT is mentioned for the first time in the Discussion. Suggest this be brought up earlier in the introduction to frame the reason to do the study.

-Discussion mentions WHO policy is in that setting with generalized epidemics that routine PITC should be offered to all with presumptive or diagnosed TB. Do the Malawian guidelines agree with this?

-The statistic that >50% of clinic attenders in the study reported TB symptoms is an important one and I’d suggest that this be mentioned in abstract.

-Authors mention that only 44% of participants underwent exit interview as a limitation. One way to overcome this limitation is to include data from registers from the study period regarding TB symptoms (if available), HIV testing offer, and HIV test result. The latter 2 should be in the register.

-Given the data, what do the authors suggest are the next steps?

References

-A minor comment, but please use consistent formatting/spacing in the references.

Table 1

Was any statistical testing done to see if there were differences between adult clinic attendees who had an exit interview or not. Suggest this is done. It appears that overall a lower proportion of participants who had a positive symptom screen underwent an exit interview.

Figure 1

For the top row of graphs please label Men and Women if that is what the Y axis is.

Reviewer #2: Authors have presented a nice study. They were interested to find out if adult patients seeking urgent care with TB-symptoms would receive PITC (as is recommended by WHO and Malawi National programmes).

Elegantly, they made their observations independent of the care offered at the health care facility (staffed by clinical officer, and nurses). Investigators positioned themselves at a registration desk for adult outpatients. Following verbal consent, identified patients through fingerprint biometrics and asked questions about age, HIV testing history, and TB symptoms.

Then, during exit interviews, 44% of adult patients were linked and patients were asked if an HIV test was offered, and if a test was taken.

Their data showed that contrary to their expectation, patients with TB symptoms were less likely to be tested than patients without TB patients. They also did statistical modeling to predict who would be more likely to be HIV tested.

The findings are clearly presented. This will be a useful contribution to the literature.

I have the following questions that should be addressed in the revision.

1. Participants were asked if they had ever previously tested for HIV. Can authors clarify if they collected the date of the last HIV test? If they did not, then mention this as a study limitation. If they did, they can provide the proportion who tested in the last year (annual testing for adults of the general population is a WHO recommendation).

2. Participants were asked their self-reported HIV status and ART status. HIV-positive patients on ART were excluded from the modeling. Can authors present the number of newly diagnosed patients (by self-report)? There should be patients who will have mentioned this, and thee majority will/should have started same day treatment. Unless authors plan to report on self-reported test outcome - but they should say something about self-reported HIV testing at care seeking (as they asked about it). Is it possible that patients with a new HIV diagnosis who were started on ART were not interested to present the exit desk for interview? This should be mentioned as a limitation of this study.

3. Qualitative data (e.g. focus group discussions with providers) were not collected. I find this another important limitation of the study. It would have been so easy to present result back to providers and ask them why they through that younger patients, men, and patients without TB symptoms were more like to be HIV tested.

Other points that can be clarified / improved upon:

1. Discussion hinges on two arguments - leading to two proposed strategies. Poor performance of PITC should be improved through targeted testing and ROOT (routine opt out testing).

Poor performance: Vast numbers of patients with TB-symptoms are not tested. These are major missed opportunities. Rather than calling this "suboptimal" - be more bold in your conclusion! This is very poor implementation of existing guidelines. Why is that so? that remains unclear. Authors suggest that targeted PITC could be achieved through oral self-testing.

ROOT is presented as a possible if not best strategy. Is this likely? Given that current system under performs?

Perhaps authors can more clearly distinguish the two strategies. Something like -- targeted PITC should be immediately implemented. ROOT is the preferred strategy but would require substantial resources.

Small points:

PITC HIV testing - misnomer - change to targeted HIV testing.

Is there a reference for ROOT?

Participants with a self-reported HIV testing history may drive them to request further HIV testing. Was this not explored in the exit interview? Were you offered an HIV test? Did you take an HIV test? or Did you ask for an HIV test yourself?

first paragraph discussion - last sentence. Optimism can be taken from an increase of 89.9% to 90.8%. There is either a typo in the stats, but i find this a minimal increase not worth discussing and no reason for optimism.

Last sentence of introduction (stratification by sex) reads as a methods sentence and is better placed in methods.

Approximately 1 in 4 patients is offered testing. And of those offered, 4 out of 5 accept HIV testing. Is it clear why a substantial number of patients refuse testing?

End.

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Reviewer #1: No

Reviewer #2: Yes: Eduard Sanders

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PONE-D-19-35399R1

Provider-initiated HIV testing and TB screening in the era of universal coverage: are the right people being reached? A cohort study in Blantyre, Malawi

PLOS ONE

Dear Dr. Mair,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has improved in clarity but still 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 see the specific suggestions from Reviewer 1 about additional clarification and some minor edits that would improve readability.

We would appreciate receiving your revised manuscript by Jul 02 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Susan Marie Graham, MD, MPH, PhD

Academic Editor

PLOS ONE

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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: (No Response)

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: 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: Yes

Reviewer #2: Yes

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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: (No Response)

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. 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: Overall much improved. Suggests/comments follow.

Abstract

Clarify that this was among clinic attendees with acute illness. Dates are typically spelled out, but leave this style issue to the editors. Could consider simplifying abstract with regards to the categories of symptoms- since participants with and without symptoms the proportion offered testing was the same, why not just say among participants with any TB symptoms (especially since there appeared to be no difference among each specific symptom).

Agree with the conclusion of the Abstract.

Introduction

-Perhaps mention that Malawi is not one of the 7 countries to meet this 90/90/90 target.

-Add reference for ROOT and oral testing

Methods

-Provide reference of the Malawi national HIV Programme guidelines.

-Be explicit that patients with known HIV on ART were excluded in the Methods.

-Research assistant should be lower case I believe.

-What does opportunistic manner mean?

-Please be consistent with references either before or after a period.

-Not sure why there is a page break after Data and reproducability and Results?

Results

-Provide % for the 276 attenders who were HIV+ on ART that were excluded.

-Strikingly low offer of HIV testing (27.6%). (comment only)

-Striking that participants with a previous history of TB weren’t offered HIV testing. (comment only).

-Among those offered but not tested, what was the reason?

Discussion

-Please be careful with punctuation (2 periods at end of firs sentence in Discussion)

-Seems important to point out in the first paragraph of the discussion that this low rate of testing is despite the national guideline recommendations.

-ROOT already defined in Introduction, consider using only abbreviation here.

-Were there test kit stockouts during the time? It’s mentioned as a potential reason, but no further discussion.

-Although oral testing is a fantastic idea- why do the authors think this would increase testing? What does semi-supervised mean in regards to oral testing?

References

-Still has inconsistent formatting with references (some with hanging indent, some not).

-I’m a bit surprised that one of the national guideline referenced is from 2012.

Table 1

-Please use consistent capitalization for row headers.

-What are the numbers separated by a comma? Are they IQR? Ranges? Please specific in the table.

Table 2

Define WAIC

Reviewer #2: authors may want to check the following added sentence in their discussion:

"Qualitative research has suggested that patients often wish to know their status due a

period of health and therefore may be motivated to test themselves"

Not clear what is meant by a period of health

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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.

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Reviewer #1: No

Reviewer #2: Yes: Eduard Sanders

[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 to be viewed.]

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Provider-initiated HIV testing and TB screening in the era of universal coverage: are the right people being reached? A cohort study in Blantyre, Malawi

PONE-D-19-35399R2

Dear Dr. Mair,

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.

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Kind regards,

Susan Marie Graham, MD, MPH, PhD

Academic Editor

PLOS ONE

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Reviewers' comments: