Evidence map›Paper›PMID 33206462›Full record

ArticleJournal of the International AIDS Society2020

Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial.

Elizabeth R Brown, Craig W Hendrix, Ariane van der Straten, Flavia M Kiweewa, Nyaradzo M Mgodi, Thesla Palanee-Philips, Mark A Marzinke, Linda-Gail Bekker, Lydia Soto-Torres, Sharon L Hillier and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of the International AIDS Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 10% of its field
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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.

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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

12 authors at 8 institutions in 4 countries.

Elizabeth R BrownVaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0003-4286-2111
Craig W HendrixDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-5696-8665
Ariane van der StratenWomen's Global Health Imperative, RTI International, San Francisco, CA, USA.ORCID 0000-0001-8536-648X
Flavia M KiweewaMakerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.ORCID 0000-0002-0046-4353
Nyaradzo M MgodiUniversity of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe.
Thesla Palanee-PhilipsWits Reproductive Health and HIV Research Institute, School of Clinical Medicine, University of the Witswatersrand, Johannesburg, South Africa.
Mark A MarzinkeDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Linda-Gail BekkerDesmond Tutu HIV Foundation Clinical Research Site, Cape Town, South Africa.ORCID 0000-0002-0755-4386
Lydia Soto-TorresDivision of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Sharon L HillierDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and Magee-Womens Research Institute, Pittsburgh, PA, USA.
Jared M BaetenDepartments of Medicine, Epidemiology, and Global Health, University of Washington, Seattle, WA, USA.ORCID 0000-0001-8242-8438
MTN-020/ASPIRE Study Team
Johns Hopkins University · USUniversity of Washington · USDesmond Tutu HIV Foundation · ZAMUJHU Research Collaboration · UGNational Institutes of Health · USRTI International · USUniversity of Pittsburgh · USUniversity of Zimbabwe · ZW

Funding

Microbicide Trials NetworkUM1AI068633 · NIAID · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI HILLIER, SHARON L. · 2011 to 2021
$175.0M
UZ-UCSF CTUUM1AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZVAVAHERA MIKE CHIRENJE, LYNDA STRANIX-CHIBANDA · 2012 to 2026
$75.9M
Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Statistical and Data Management Center (SDMC): Microbicide Trials NetworkUM1AI068615 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BROWN, ELIZABETH RENATA · 2011 to 2021
$66.5M
WG3: HIV, Co-infections and Co-morbiditiesP30AI036219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI Alan David Levine · 1994 to 2026
$50.0M
UZ-UCSF Clinical Trials UnitU01AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIRENJE, ZVAVAHERA MIKE · 2007 to 2011
$49.3M
The Johns Hopkins University - Uganda Clinical Trials UnitUM1AI069530 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARY Glenn Fowler, Philippa Musoke · 2012 to 2026
$34.8M
Wits HIV Research Group CLINICAL TRIAL UNIT (CTU) reapplicationUM1AI069463 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI REES, HELEN, SANNE, IAN MATTHIAS · 2012 to 2025
$31.8M
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
NIAID NIH HHS P30 AI036219NIAID NIH HHS P30 AI094189NIAID NIH HHS U01 AI069436NIAID NIH HHS UM1 AI068615NIAID NIH HHS UM1AI068615NIAID NIH HHS UM1 AI068633NIAID NIH HHS UM1AI068633NIAID NIH HHS UM1 AI069436NIAID NIH HHS UM1 AI069463NIAID NIH HHS UM1 AI069530NIAID NIH HHS UM1 AI106707NIAID NIH HHS UM1AI106707
6 · The paper itself

Abstract

introductionA vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women's risk of sexually acquiring HIV-1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use.

methodsWe measured the amount of dapivirine in returned rings from a placebo-controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non-use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time-dependent covariate for HIV-1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV-1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence.

resultsResidual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV-1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV-1 acquisition estimated 75% to 91% HIV-1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall.

conclusionsResidual dapivirine levels, an objective measure of adherence, were correlated with HIV-1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long-acting, woman-initiated approach for discreet HIV-1 prevention.

Indexed as

Contraceptive Devices, FemaleHIV-1AdolescentAdultAnti-HIV AgentsDrug LiberationFemaleHIV InfectionsHumansMedication AdherenceMiddle AgedPre-Exposure ProphylaxisPyrimidinesRandomized Controlled Trials as TopicRisk Reduction BehaviorSexual BehaviorAnti-HIV AgentsDapivirinePyrimidinesadherenceAfricaclinical trialsHIV preventionHIV prevention trialswomen

Identifiers

PMID33206462
PMCPMC7673220
OpenAlexW3103664144

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.