Evidence map›Paper›PMID 35134180›Full record

ArticleThe Journal of infectious diseases2022

Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants.

Robert A Smith, Vincent H Wu, Jennifer Song, Dana N Raugi, Khardiata Diallo Mbaye, Moussa Seydi, Geoffrey S Gottlieb

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

6 citing papers in PubMed, 7 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

7 authors at 2 institutions in 2 countries.

Robert A SmithCenter for Emerging and Reemerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Vincent H WuCenter for Emerging and Reemerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Jennifer SongCenter for Emerging and Reemerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Dana N RaugiCenter for Emerging and Reemerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Khardiata Diallo MbayeService des Maladies Infectieuses et Tropicales, Centre Hospitalier National Universitaire de Fann, Dakar, Senegal.
Moussa SeydiService des Maladies Infectieuses et Tropicales, Centre Hospitalier National Universitaire de Fann, Dakar, Senegal.
Geoffrey S GottliebCenter for Emerging and Reemerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
University of Washington · USCentre Hospitalier National Universitaire de Fann · SN

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 InfectionR01AI120765 · NIAID · UNIVERSITY OF WASHINGTON · PI Geoffrey Scott Gottlieb · 2015 to 2026
$8.9M
HIV Drug Resistance DatabaseR24AI136618 · NIAID · STANFORD UNIVERSITY · PI ROBERT William SHAFER · 2018 to 2026
$7.3M
NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI120765NIAID NIH HHS R24 AI136618
6 · The paper itself

Abstract

backgroundIntegrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations that emerge in HIV-2 in response to INIs are incompletely characterized.

methodsWe performed systematic searches of GenBank and HIV-2 drug resistance literature to identify treatment-associated mutations for phenotypic evaluation. We then constructed a library of 95 mutants of HIV-2ROD9 that contained single or multiple amino acid changes in the integrase protein. Each variant was tested for susceptibility to raltegravir and dolutegravir using a single-cycle indicator cell assay.

resultsWe observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2ROD9. HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the half maximum effective concentration (EC50) for raltegravir when introduced into 1 or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance. HIV-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs.

conclusionsOur analysis demonstrates the contributions of novel INI-associated mutations to raltegravir and dolutegravir resistance in HIV-2. These findings should help to improve algorithms for genotypic drug resistance testing in HIV-2-infected individuals.

Indexed as

Anti-HIV AgentsHIV-1HIV InfectionsHIV IntegraseHIV Integrase InhibitorsDolutegravirDrug Resistance, ViralHeterocyclic Compounds, 3-RingHIV-2HumansMutationOxazinesPiperazinesPyridonesRaltegravir PotassiumAnti-HIV AgentsDolutegravirHeterocyclic Compounds, 3-RingHIV IntegraseHIV Integrase InhibitorsOxazinesp31 integrase protein, Human immunodeficiency virus 2PiperazinesPyridonesRaltegravir Potassiumantiretroviral therapydolutegravirdrug resistanceHIV-1HIV-2raltegravir

Identifiers

PMID35134180
PMCPMC9417127
OpenAlexW4210444418

What OpenQuestion holds

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Registered trials

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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.