PONE-D-23-42740Preferences for Oral and Injectable PrEP among qualitative sub-study participants in HPTN 084PLOS ONE

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Overall support for the HIV Prevention Trials Network (HPTN) is provided by the National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Allergy and Infectious Diseases (NIAID) (nih.gov), Office of the Director (OD) NIH Office of the Director | National Institutes of Health (NIH), National Institutes of Health (NIH) National Institutes of Health (NIH) | Turning Discovery Into Health, National Institute on Drug Abuse (NIDA) NIDA.NIH.GOV | National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH) NIMH » Home (nih.gov), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Homepage | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development (nih.gov) under Award Numbers UM1AI068619 (HPTN Leadership and Operations Center), UM1AI068617 (HPTN Statistical and Data Management Center), and UM1AI068613 (HPTN Laboratory Center). Additional funding was provided by the Bill & Melinda Gates Foundation Bill & Melinda Gates Foundation | Bill & Melinda Gates Foundation., ViiV Healthcare The Global specialist company in HIV Care | ViiV Healthcare, and Gilead Sciences gilead.com provided pharmaceutical support.

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This study was made possible through funding support from the National Institute of Allergy and Infectious Diseases, Office of the Director, National Institutes of Health (NIH), National Institute on Drug Abuse, and the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional funding was provided by the Bill & Melinda Gates Foundation, Gilead Sciences, and ViiV Healthcare. Pharmaceutical support was provided by ViiV Healthcare and Gilead Sciences. We wish to acknowledge the contribution of the participants, their families and communities, and the community advisory boards at the four sites participating in the qualitative sub-study. We acknowledge the contribution of the HPTN 084 study team.  Shout out the SCHARP data team!

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Overall support for the HIV Prevention Trials Network (HPTN) is provided by the National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Allergy and Infectious Diseases (NIAID) (nih.gov), Office of the Director (OD) NIH Office of the Director | National Institutes of Health (NIH), National Institutes of Health (NIH) National Institutes of Health (NIH) | Turning Discovery Into Health, National Institute on Drug Abuse (NIDA) NIDA.NIH.GOV | National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH) NIMH » Home (nih.gov), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Homepage | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development (nih.gov) under Award Numbers UM1AI068619 (HPTN Leadership and Operations Center), UM1AI068617 (HPTN Statistical and Data Management Center), and UM1AI068613 (HPTN Laboratory Center). Additional funding was provided by the Bill & Melinda Gates Foundation Bill & Melinda Gates Foundation | Bill & Melinda Gates Foundation., ViiV Healthcare The Global specialist company in HIV Care | ViiV Healthcare, and Gilead Sciences gilead.com provided pharmaceutical support.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: N/A

Reviewer #2: Yes

Reviewer #3: N/A

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: The acceptability and individual preference of PrEP modalities will become more and more important as more PrEP products become available and research shifts to implementation. This work is a very important contribution highlighting the importance of considering not only stigma, but also practicability, short and long term side effects as well as monetary considerations.

My only major comment is that I would like to see a bit more quantitative analysis. For each pattern that is highlighted in the "findings" section, you should indicate how many respondents were asked a similar question. Sometimes this information is given and sometimes it is not or it is given only vaguely (about one third). I feel that we get a good quantitative breakdown of concerns prior to receiving injections, but it would be good to see how that compares with what was found.

I think this is especially important as these IDI transcripts will not be made publicly available due to justifiable privacy concerns.

Very minor comments:

Background

Line 64 “The jury is still out” suggest rephrasing to more precise language. Perhaps “numerous demonstration projects and implementation studies show that PrEP adherence among women is typically not sufficient to achieve complete protection” and citing Marrazzo (2024) on this point.

Generally, seems like some of these authors have done more work on this research question that should be highlighted in the introduction. Velloza et al (10.1002/jia2.25463) specifically addressed reasons for non-adherence on HPTN082.

Findings

Line 196 “By far, women appreciated the ease and convenience of a long-acting formulation” relative to an oral formulation?

Reviewer #2: This is a well written and interesting mixed methods manuscript that is important contribution to the literature as long-acting antiretrovirals are implemented in southern Africa. I only have minor comments for the authors to consider.

Introduction

Would recommend that the authors not use the trade names for TDF/FTC and TAF/FTC through out the manuscript. TDF is defined on line 45, but TAF/FTC is not (line 48).

Line 64: Would consider revising “the jury is still out” to something more descriptive such as “it has not been full evaluated”.

Line 70: Would include the full enrolled cohort, and not “> 3,200”

Methods

The methods are clear and outline the qualitative and quantitative approach for this analysis.

Results

The results are well written and clear. The section on injection site pain was a little confusion, which seems to be secondary to the wording of the second sentence on lines 225-226 Perhaps change to “Some participants described the pain as easily tolerable”.

Discussion

The discussion is well written and clear.

Reviewer #3: This manuscript used survey and qualitative data from a four-country sub-study in the HPTN 084 study to examine oral and injectable PrEP acceptability and considerations for CAB access among African women.

One of the key findings is “Participants overwhelmingly preferred injections to pills, ap- preciating the ease, convenience, and privacy of a long-acting formulation. ” However, such a finding is not fully demonstrated in the FINDINGS section. Specifically, the only relevant description is simply one sentence “Regardless of study arm, most women in the sub-study pre- ferred injections to daily pills when asked to indicate their preference; they often explained that the injection would be harder to forget to take and meant fewer clinic visits. ” I would suggest to include more details (e.g., proportion of women that prefer injection, quotes on forgetting taking PrEP and clinic visits)to strengthen the statement.

Some other comments:

1. Abstract: what do you mean by “A study statistician identified participants’ assigned study arm”?

2. Are the CPs also representative of early, mid-trial, or later entry? It is not clear from the description in the manuscript.

3. The SCs received up to two serial interviews. When are those interviews taken? Line 126: “Qualitative analyses presented in this paper focus on the first and second IDIs, both of which were conducted prior to participants’ ability to switch or remain on their current active product, i.e., during the blinded and unblinded periods of the study.” Is this statement also correct for the SCs?

4. Line 291: “Less frequently (but more often than for injections), women listed an array 1

of side effects they attributed to oral pill use. ” What is the frequency for side effect for those randomized to the CAB arm? Can you add the number to Line 271?

5. Minor comments:

• Line 99: “from” should be removed?

• Line 239: “single” is used for this women instead of “not married” by others.

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Reviewer #1: Yes: Mia Moore

Reviewer #2: No

Reviewer #3: No

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Preferences for Oral and Injectable PrEP among qualitative sub-study participants in HPTN 084

PONE-D-23-42740R1

Dear Dr. Tolley,

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Kind regards,

Tinashe Mudzviti, MPhil(MD)

Academic Editor

PLOS ONE

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