Evidence map›Paper›PMID 26392486›Full record

ArticleAntimicrobial agents and chemotherapy2015

The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

Robert A Smith, Dana N Raugi, Vincent H Wu, Sally S Leong, Kate M Parker, Mariah K Oakes, Papa Salif Sow, Selly Ba, Moussa Seydi, Geoffrey S Gottlieb and 1 more

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Antimicrobial agents and chemotherapy · 2018
    Article
  11. 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

11 authors at 2 institutions in 2 countries.

Robert A SmithCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA smithra@u.washington.edu.
Dana N RaugiCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Vincent H WuCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Sally S LeongCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Kate M ParkerCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Mariah K OakesCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Papa Salif SowService des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal.
Selly BaService des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal.
Moussa SeydiService des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal.
Geoffrey S GottliebCenter for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
University of Washington-Dakar HIV-2 Study Group
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 Kenneth Sherr · 1988 to 2026
$104.9M
XRAY CRYSTALLOGRAPHIC STRUCTURE ANALYSIS: PROTEIN SORTINGP41RR001081 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 1985 to 2011
$17.6M
Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 InfectionR01AI120765 · NIAID · UNIVERSITY OF WASHINGTON · PI Geoffrey Scott Gottlieb · 2015 to 2026
$8.9M
Antiretroviral Therapy for HIV-2 Infection in SenegalR01AI060466 · NIAID · UNIVERSITY OF WASHINGTON · PI GOTTLIEB, GEOFFREY SCOTT · 2005 to 2014
$6.5M
NCRR NIH HHS NIH P41 RR-01081NCRR NIH HHS P41 RR001081NIAID NIH HHS 2R01-AI060466NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI060466NIAID NIH HHS R01 AI120765NIAID NIH HHS R01AI120765
6 · The paper itself

Abstract

Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.

Indexed as

Anti-HIV AgentsCell LineDrug Resistance, ViralHIV-1HIV-2HIV Reverse TranscriptaseHumansModels, MolecularMutagenesis, Site-DirectedProtein ConformationReverse Transcriptase InhibitorsStavudineThymidineAnti-HIV AgentsBMS-986001HIV Reverse Transcriptasereverse transcriptase, Human immunodeficiency virus 2Reverse Transcriptase InhibitorsStavudineThymidine

Identifiers

PMID26392486
PMCPMC4649195
OpenAlexW2341929619

What OpenQuestion holds

Textmetadata
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.