Evidence map›Paper›PMID 38838028›Full record

Trial reportPloS one2024

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

Sharon L Achilles, Clifton W Kelly, Craig J Hoesley, Diana L Blithe, Jill Brown, Barbra A Richardson, Brid Devlin, Craig W Hendrix, Samuel M Poloyac, Mark A Marzinke and 7 more

Abstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Preventing HIV in women in Africa.Nature medicine · 2025
    Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Sharon L AchillesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID https://orcid.org/0000-0002-7478-8262
Clifton W KellyStatistical Center for HIV/AIDS Research & Prevention, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.
Craig J HoesleyUniversity of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States of America.
Diana L BlitheNational Institute of Child Health and Human Development, Contraceptive Development Program, DIPHR, NIH, Bethesda, Maryland, United States of America.
Jill BrownNational Institute of Child Health and Human Development, Contraceptive Development Program, DIPHR, NIH, Bethesda, Maryland, United States of America.ORCID https://orcid.org/0000-0003-1615-4584
Barbra A RichardsonStatistical Center for HIV/AIDS Research & Prevention, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.
Brid DevlinInternational Partnership for Microbicides, Silver Spring, Maryland, United States of America.
Craig W HendrixDepartment of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Samuel M PoloyacDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Mark A MarzinkeDepartment of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Holly GundackerStatistical Center for HIV/AIDS Research & Prevention, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.
Devika SinghMagee-Womens Research Institute, Pittsburgh, Pennsylvania, United States of America.
Jeanna M PiperNational Institutes of Allergy and Infectious Disease, NIH, Bethesda, Maryland.
Sherri JohnsonFHI 360, Durham, North Carolina, United States of America.
John SteytlerInternational Partnership for Microbicides, Silver Spring, Maryland, United States of America.
Beatrice A ChenDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID https://orcid.org/0000-0002-4437-4632
MTN-030/IPM 041 and MTN-044/IPM 053/CCN019 Protocol Teams for the Microbicide Trials Network and the Contraceptive Clinical Trials Network

Funding

SDMC: HPTN 084 Pregnancy SupplementUM1AI068617 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Elizabeth Renata Brown, Deborah J Donnell · 2011 to 2026
$204.9M
Microbicide Trials NetworkUM1AI068633 · NIAID · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI HILLIER, SHARON L. · 2011 to 2021
$175.0M
Statistical and Data Management Center (SDMC): Microbicide Trials NetworkUM1AI068615 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BROWN, ELIZABETH RENATA · 2011 to 2021
$66.5M
Laboratory Center (LC): Microbicide Trials NetworkUM1AI106707 · NIAID · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI MELLORS, JOHN W, ROHAN, LISA CENCIA · 2014 to 2021
$27.1M
Development of novel contraceptive methods for men and womenZIBHD008987 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BLITHE, DIANA · 2019 to 2025
$7.2M
NIAID NIH HHS UM1 AI068615NIAID NIH HHS UM1 AI068617NIAID NIH HHS UM1 AI068633NIAID NIH HHS UM1 AI106707NICHD NIH HHS HHSN275201200002CNICHD NIH HHS HHSN275201200002I
6 · The paper itself

Abstract

backgroundVaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy.

methodsTwo phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use. MTN-044/IPM 053/CCN019 compared continuous or cyclic use of the DPV/LNG ring over 90 days of use. Safety was assessed by recording adverse events (AEs). DPV and LNG concentrations were quantified in plasma, cervicovaginal fluid, and cervical tissue. Vaginal bleeding was self-reported.

resultsThere were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs with DPV/LNG ring vs. DPV ring use (p = .22), or with DPV/LNG ring continuous vs. cyclic use (p = .67). Higher plasma DPV concentrations were observed in users of DPV/LNG compared to DPV-only rings (Cmax p = 0.049; AUC p = 0.091). Plasma DPV and LNG concentrations were comparable with continuous and cyclic use (Cmax p = 0.74; AUC p = 0.25). With cyclic use, median nadir plasma DPV concentration was approximately 300 pg/mL two days after removal and median t1/2 for cervicovaginal fluid DPV concentration was 5.76 hours (n = 3). Overall bleeding experiences did not differ between continuous and cyclic users (p = 0.12).

conclusionsThe extended duration DPV/ LNG rings were well tolerated and the observed DPV concentrations in plasma and cervicovaginal fluid when used continuously exceeded concentrations observed in previous DPV ring efficacy studies. LNG concentrations in plasma were comparable with other efficacious LNG-based contraceptives. Genital DPV concentrations had a short half-life and were thus not well sustained following ring removal.

Indexed as

Contraceptive Devices, FemaleLevonorgestrelPyrimidinesUterine HemorrhageAdultAnti-HIV AgentsFemaleHIV InfectionsHumansMiddle AgedYoung AdultAnti-HIV AgentsDapivirineLevonorgestrelPyrimidines

Identifiers

PMID38838028
PMCPMC11152307

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.