Evidence map›Paper›PMID 39861910›Full record

ArticleViruses2025

Comparative Analyses of Antiviral Potencies of Second-Generation Integrase Strand Transfer Inhibitors (INSTIs) and the Developmental Compound 4d Against a Panel of Integrase Quadruple Mutants.

Steven J Smith, Xue Zhi Zhao, Stephen H Hughes, Terrence R Burke

Abstract readComparative Study
In one paragraph

Article in Viruses, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

4 authors.

Steven J SmithChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.ORCID 0000-0001-9207-1671
Xue Zhi ZhaoChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.ORCID 0000-0003-1006-6364
Stephen H HughesHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.ORCID 0000-0002-9176-4377
Terrence R BurkeChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.ORCID 0000-0001-9925-8586

Funding

PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
DESIGN AND SYNTHESIS OF HIV INTEGRASE INHIBITORS AS POTENTIAL ANTI-AIDS DRUGSZ01BC007363 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BURKE, TERRENCE · 1996 to 2008
$609k
Intramural NIH HHS Z01 BC006150Intramural NIH HHS Z01 BC007363
6 · The paper itself

Abstract

Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance. Herein, we evaluated the antiviral potencies of our lead developmental INSTI 4d and the second-generation INSTIs dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) against a panel of IN quadruple mutants. The mutations are centered around G140S/Q148H, including positions L74, E92, and T97 combined with E138A/K/G140S/Q148H. All of the tested INSTIs lose potency against these IN quadruple mutants compared with the wild-type IN. In single-round infection assays, compound 4d retained higher antiviral potencies (EC

Indexed as

Antiviral AgentsHIV-1HIV IntegraseHIV Integrase InhibitorsAmidesCOVID-19 Drug TreatmentDiketopiperazinesDolutegravirDrug Resistance, ViralHeterocyclic Compounds, 3-RingHumansMutationNaphthyridinesOxazinesPiperazinesPyridonesAmidesAntiviral AgentsbictegravircabotegravirDiketopiperazinesDolutegravirHeterocyclic Compounds, 3-RingHIV IntegraseHIV Integrase InhibitorsNaphthyridinesOxazinesPiperazinesPyridonesintegrasemutantsmutationspotencyresistance

Identifiers

PMID39861910
PMCPMC11768864

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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.