Evidence map›Paper›PMID 31280314›Full record

SynthesisThe Journal of antimicrobial chemotherapy2019

A systematic review of the genetic mechanisms of dolutegravir resistance.

Soo-Yon Rhee, Philip M Grant, Philip L Tzou, Geoffrey Barrow, P Richard Harrigan, John P A Ioannidis, Robert W Shafer

Open access · bronzeAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 3 pooled it
10.1field-weighted citation impact, top 1% 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

99 citing papers in PubMed, 3 syntheses or guidelines pooled it, 150 citations in OpenAlex.

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  11. Patterns of HIV-1 Viral Load Suppression and Drug Resistance During the Dolutegravir Transition: A Population-based Longitudinal Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
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39 more citing papers are in PubMed but not listed here.

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 3 institutions in 3 countries.

Soo-Yon RheeDepartment of Medicine, Stanford University, Stanford, CA, USA.
Philip M GrantDepartment of Medicine, Stanford University, Stanford, CA, USA.
Philip L TzouDepartment of Medicine, Stanford University, Stanford, CA, USA.
Geoffrey BarrowCentre for HIV/AIDS Research, Education and Services (CHARES), Department of Medicine, University of the West Indies, Kingston, Jamaica.
P Richard HarriganDepartment of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
John P A IoannidisDepartment of Medicine, Stanford University, Stanford, CA, USA.
Robert W ShaferDepartment of Medicine, Stanford University, Stanford, CA, USA.
Stanford University · USUniversity of British Columbia · CAUniversity of the West Indies · JM

Funding

HIV Drug Resistance DatabaseR24AI136618 · NIAID · STANFORD UNIVERSITY · PI ROBERT William SHAFER · 2018 to 2026
$7.3M
NIAID NIH HHS R24 AI136618
6 · The paper itself

Abstract

backgroundCharacterizing the mutations selected by the integrase strand transfer inhibitor (INSTI) dolutegravir and their effects on susceptibility is essential for identifying viruses less likely to respond to dolutegravir therapy and for monitoring persons with virological failure (VF) on dolutegravir therapy.

methodsWe systematically reviewed dolutegravir resistance studies to identify mutations emerging under dolutegravir selection pressure, the effect of INSTI resistance mutations on in vitro dolutegravir susceptibility, and the virological efficacy of dolutegravir in antiretroviral-experienced persons. RESULTS AND

conclusionsWe analysed 14 studies describing 84 in vitro passage experiments, 26 studies describing 63 persons developing VF plus INSTI resistance mutations on a dolutegravir-containing regimen, 41 studies describing dolutegravir susceptibility results, and 22 clinical trials and 16 cohort studies of dolutegravir-containing regimens. The most common INSTI resistance mutations in persons with VF on a dolutegravir-containing regimen were R263K, G118R, N155H and Q148H/R, with R263K and G118R predominating in previously INSTI-naive persons. R263K reduced dolutegravir susceptibility ∼2-fold. G118R generally reduced dolutegravir susceptibility >5-fold. The highest levels of reduced susceptibility occurred in viruses containing Q148 mutations in combination with G140 and/or E138 mutations. Dolutegravir two-drug regimens were highly effective for first-line therapy and for virologically suppressed persons provided dolutegravir's companion drug was fully active. Dolutegravir three-drug regimens were highly effective for salvage therapy in INSTI-naive persons provided one or more of dolutegravir's companion drugs was fully active. However, dolutegravir monotherapy in virologically suppressed persons and functional dolutegravir monotherapy in persons with active viral replication were associated with a non-trivial risk of VF plus INSTI resistance mutations.

Indexed as

MutationAnimalsClinical Trials as TopicDolutegravirDrug Resistance, ViralHeterocyclic Compounds, 3-RingHIV-1HIV InfectionsHIV Integrase InhibitorsHumansMiceOxazinesPiperazinesPyridonesVirus ReplicationDolutegravirHeterocyclic Compounds, 3-RingHIV Integrase InhibitorsOxazinesPiperazinesPyridones

Identifiers

PMID31280314
PMCPMC6798839
OpenAlexW2954620310

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.