Evidence map›Paper›PMID 36345569›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023

Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction.

John Steytler, Charles Craig, Elna van der Ryst, Ben Van Baelen, Jeremy Nuttall, Neliëtte van Niekerk, John Mellors, Urvi Parikh, Carole Wallis, Ring Study and the DREAM Trial Study Teams

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 42% 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.

NCT01539226 nacompletednot on this map

A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women

TypeinterventionalSponsorInternational Partnership for Microbicides, Inc.Ran2012 to 2016Enrolled1,959ConditionsHIV InfectionsArmsPlacebo Vaginal Ring, Dapivirine Vaginal Ring, 25 mg
NCT02862171 phase3completednot on this map

A Follow-On, Open-Label Trial To Assess Continued Safety Of And Adherence To The Dapivirine (25 Mg) Vaginal Ring-004 In Healthy, HIV-Negative Women

TypeinterventionalSponsorInternational Partnership for Microbicides, Inc.Ran2016 to 2019Enrolled941ConditionsHIV PreventionArmsDapivirine Vaginal Ring-004
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Trial
  2. Trial
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

10 authors at 6 institutions in 4 countries.

John SteytlerInternational Partnership for Microbicides South Africa NPC, Johannesburg, South Africa.
Charles CraigResearch Virology Consulting Ltd, Cambridgeshire, United Kingdom.
Elna van der RystIndependent Consultant, Kent, United Kingdom.
Ben Van BaelenBVB Clin Consult BVBA, Herent, Belgium.
Jeremy NuttallInternational Partnership for Microbicides, Silver Spring, Maryland, USA.
Neliëtte van NiekerkInternational Partnership for Microbicides South Africa NPC, Johannesburg, South Africa.
John MellorsMicrobicide Trials Network Virology Core Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Urvi ParikhMicrobicide Trials Network Virology Core Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Carole WallisBio-Analytical Research Corporation Laboratory and Lancet Laboratories, Johannesburg, South Africa.
Ring Study and the DREAM Trial Study Teams
International Partnership for Microbicides · USUniversity of Pittsburgh · USClinvest (United States) · USKent County Council · GBLancet Laboratories · ZAPA Consulting Group · GB

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
NCI NIH HHS P30 CA047904
6 · The paper itself

Abstract

backgroundThe Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas the Dapivirine Ring Extended Access and Monitoring (DREAM) trial, approximated a 62% risk reduction. The observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) and effects on viral susceptibility are described here.

methodsPopulation-based genotyping on plasma samples collected longitudinally, and next-generation sequencing (NGS) and phenotypic susceptibility testing were done on plasma collected at seroconversion. Retrospective HIV-1 RNA testing was used to more accurately establish the time of infection.

resultsIn the Ring Study, NNRTI RAMs were not observed in most viruses at seroconversion (population-based genotyping: DVR: 71 of 84, 84.5%; placebo: 50 of 58, 86.2%). However, more E138A was found in the DVR group (E138A DVR: 9 of 84, 10.7%; placebo: 2 of 58, 3.4%; P = .2, Fisher exact test). NGS detected 1 additional mutation in each group (DVR: G190A; placebo: G190A and G190E). Marginal dapivirine susceptibility reduction was found with NNRTI RAMs at seroconversion (geometric mean fold-change, range: DVR, 3.1, 1.3-5.1; placebo, 5.8, 0.9-120). NNRTI RAMs were not emergent between first detectable HIV-1 RNA and seroconversion when these visits differed (paired samples, mean ring use: DVR, n = 52, 35 days; placebo, n = 26, 31 days). After stopping DVR, 2 of 63 viruses had emergent G190G/A or K103K/N with V106V/M at final study visit. Resistance profiles from the DREAM trial were consistent with the Ring Study.

conclusionsDVR showed little potential for selection of NNRTI-resistant variants. CLINICAL TRIALS REGISTRATION: NCT01539226 and NCT02862171.

Indexed as

Anti-HIV AgentsContraceptive Devices, FemaleHIV-1HIV InfectionsHIV SeropositivityFemaleHumansPyrimidinesRetrospective StudiesReverse Transcriptase InhibitorsRNAAnti-HIV AgentsDapivirinePyrimidinesReverse Transcriptase InhibitorsRNAantiretroviral drug susceptibilityDapivirine vaginal ring-004HIV-1preexposure prophylaxis

Identifiers

PMID36345569
PMCPMC12097997
OpenAlexW4308552315

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.