PONE-D-23-39000Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): implications for multipurpose prevention technology developmentPLOS ONE

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: This manuscript presents acceptability data on the dapivirine levonorgestrel (DPV-LNG) ring from two randomized trials of non-pregnant cisgender women without HIV at the University of Pittsburgh and University of Alabama. Overall, most participants (n=21/23) in a randomized study offering DPV-LNG versus solely DVR for 14 days liked the ring modality they were offered, with no significant difference in acceptability between arm offered DPV-LNG versus DVR-only ring. About half (n=13/25) in the study offering DPV-LNG for 90 days liked the DPV-LNG ring. Those who disliked the ring in MTN-044 reported significantly higher incidence of unanticipated vaginal bleeding, and ring expulsion was reported more frequently by women who disliked the DPV-LNG ring.

The overall study is well-conducted, and the authors have identified an important gap in understanding factors impacting combination ring acceptability, adherence, and persistence. The methodology is straightforward, and the results are clearly described. My feedback is described below in detail.

Major revision:

1. The described objective of the paper is to explore acceptability of the DPV-LNG ring. However, the acceptability data from MTN-030 presented in Table 3 combines data from both the DVR and DPV-LNG arms, despite much of the data interpretation related to the attributes discussed in Table 3 being separated by arm in the text (lines 309-341). Further, the abstract of the paper asserts that 21/23 women liked the DPV-LNG ring in lines 62-63, when this from my understanding is referencing combined acceptability of both ring methods offered in MTN-030. In addition to modifying this data interpretation in the abstract, would it be possible to make this clearer in Table 3, that MTN-030 is presenting acceptability of both DVR/DPV-LNG, whereas MTN-044 is presenting acceptability of only DPV-LNG options? Alternatively, would the author consider presenting solely the DPV-LNG data from MTN-030 in Table 3?

Minor revision:

1. Could you please define adherence and persistence as initially presented in line 79?

2. Lines 112-113: Was reporting effective use of condoms considered use of an effective, non-hormonal contraceptive?

3. Could you specify which of the measures described in lines 185 through 197 would measure persistence on the DPV-LNG ring, as opposed to adherence, per the above requested definitions of those terms?

Reviewer #2: Manuscript is well written and commend the researchers on this great work that is important to inform future development of MPTs.

Just minor revision on line 240, there is a punctuation sign missing after the words "due to" as it makes reading of reasons for 4 expulsions confusing when missing.

I was struck by the expulsions in MTN044 among women who experienced vaginal bleeding however good enough the authors mention data on expulsions was based off participant report as a limitation. Women experiencing these bleedings could intentionally remove the rings and report this as unintentional expulsion.

Did the participants have ring placement confirmed by attending study staff after first insertion to ensure it is in right place?

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Reviewer #1: No

Reviewer #2: No

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Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): implications for multipurpose prevention technology development

PONE-D-23-39000R1

Dear Dr. Friedland,

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Kind regards,

José das Neves

Academic Editor

PLOS ONE

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