Evidence map›Paper›PMID 21282453›Full record

ArticleAntimicrobial agents and chemotherapy2011

Human immunodeficiency virus type 1 resistance or cross-resistance to nonnucleoside reverse transcriptase inhibitors currently under development as microbicides.

Philippe Selhorst, Ana C Vazquez, Katty Terrazas-Aranda, Johan Michiels, Katleen Vereecken, Leo Heyndrickx, Jan Weber, Miguel E Quiñones-Mateu, Kevin K Ariën, Guido Vanham

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Trial
  2. Antimicrobial agents and chemotherapy · 2017
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Peptide and protein-based inhibitors of HIV-1 co-receptors.Experimental biology and medicine (Maywood, N.J.) · 2013
    Review
  8. Article
  9. Article
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  11. Article
  12. Review
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Philippe SelhorstDepartment of Microbiology, Virology Unit, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. pselhorst@itg.be
Ana C Vazquez
Katty Terrazas-Aranda
Johan Michiels
Katleen Vereecken
Leo Heyndrickx
Jan Weber
Miguel E Quiñones-Mateu
Kevin K Ariën
Guido Vanham
Instituut voor Tropische Geneeskunde · BEQuidel Corporation (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microbicides based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are currently being developed to protect women from HIV acquisition through sexual contact. However, the large-scale introduction of these products raises two major concerns. First, when these microbicides are used by undiagnosed HIV-positive women, they could potentially select for viral resistance, which may compromise subsequent therapeutic options. Second, NNRTI-based microbicides that are inactive against NNRTI-resistant strains might promote the selective transmission of these viruses. In order to address these concerns, drug resistance was selected in vitro by the serial passage of three viral isolates from subtypes B and C and CRF02_AG (a circulating recombinant form) in activated peripheral blood mononuclear cells (PBMCs) under conditions of increasing concentrations of three NNRTIs (i.e., TMC120, UC781, and MIV-160) that are currently being developed as candidate microbicides. TMC120 and MIV-160 displayed a high genetic barrier to resistance development, whereas resistance to UC781 emerged rapidly, similarly to efavirenz and nevirapine. Phenotypically, the selected viruses appeared to be highly cross-resistant to current first-line therapeutic NNRTIs (i.e., delavirdine, nevirapine, and efavirenz), although they retained some susceptibility to the more recently developed NNRTIs lersivirine and etravirine. The ability of UC781, TMC120, and MIV-160 to inhibit the in vitro-selected NNRTI-resistant viruses was also limited, although residual activity could be observed for the candidate microbicide NNRTI MIV-170. Interestingly, only four p2/p7/p1/p6/PR/RT/INT recombinant NNRTI-resistant viruses (i.e., TMC120-resistant VI829, EFV-resistant VI829, MIV-160-resistant VI829, and EFV-resistant MP568) showed impairments in replicative fitness. Overall, these in vitro analyses demonstrate that due to potential cross-resistance, the large-scale introduction of single-NNRTI-based microbicides should be considered with caution.

Indexed as

AlkynesAnilidesAnti-Infective AgentsBenzoxazinesCell LineCells, CulturedCyclopropanesDelavirdineDrug Resistance, ViralFuransGenotypeHIV-1HumansNevirapineReverse Transcriptase InhibitorsThiazolesAlkynesAnilidesAnti-Infective AgentsBenzoxazinesCyclopropanesDelavirdineefavirenzFuransMIV-160NevirapineReverse Transcriptase InhibitorsThiazolesThioamidesThioureaUC-781

Identifiers

PMID21282453
PMCPMC3067143
OpenAlexW2019853757

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.