Trial reportAntimicrobial agents and chemotherapy2021
Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains.
Trial report in Antimicrobial agents and chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Switching to Daily Doravirine/Islatravir (100/0.25 mg) Maintains Viral Suppression Through Week 48 Despite Baseline Non-Nucleoside Reverse Transcriptase Inhibitor Resistance-Associated Mutations or M184I/V in Proviral DNA.The Journal of infectious diseases · 2026Trial
- Current evidence on islatravir drug resistance and implications for future HIV treatment.Topics in antiviral medicine · 2026Review
- Unraveling the Mechanism of HIV-1 Hypersusceptibility to Tenofovir Imparted by Islatravir Resistance Mutations.bioRxiv : the preprint server for biology · 2026Article
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- Comprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.Antiviral research · 2024Article
- No antagonism or cross-resistance and a high barrier to the emergence of resistanceAntimicrobial agents and chemotherapy · 2024Article
- Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.Science advances · 2024Article
- Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- HIV-1 Resistance to Islatravir/Tenofovir Combination Therapy in Wild-Type or NRTI-Resistant Strains of Diverse HIV-1 Subtypes.Viruses · 2023Article
- HIV and Drug-Resistant Subtypes.Microorganisms · 2023Review
- How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?Current opinion in HIV and AIDS · 2022Review
- Islatravir Has a High Barrier to Resistance and Exhibits a Differentiated Resistance Profile from Approved Nucleoside Reverse Transcriptase Inhibitors (NRTIs).Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA, MK-8591, islatravir) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with exceptional potency against wild-type (WT) and drug-resistant HIV-1 in phase III clinical trials. EFdA resistance is not well characterized. To study EFdA resistance patterns that may emerge in naive or tenofovir (TFV)-, emtricitabine/lamivudine (FTC/3TC)-, or zidovudine (AZT)-treated patients, we performed viral passaging experiments starting with WT, K65R, M184V, or D67N/K70R/T215F/K219Q HIV-1. Regardless of the starting viral sequence, all selected EFdA-resistant variants included the M184V reverse transcriptase (RT) mutation. Using recombinant viruses, we validated the role for M184V as the primary determinant of EFdA resistance; none of the observed connection subdomain (R358K and E399K) or RNase H domain (A502V) mutations significantly contributed to EFdA resistance. A novel EFdA resistance mutational pattern that included A114S was identified in the background of M184V. A114S/M184V exhibited higher EFdA resistance (∼24-fold) than either M184V (∼8-fold) or A114S alone (∼2-fold). Remarkably, A114S/M184V and A114S/M184V/A502V resistance mutations were up to 50-fold more sensitive to tenofovir than was WT HIV-1. These mutants also had significantly lower specific infectivities than did WT. Biochemical experiments confirmed decreases in the enzymatic efficiency (
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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.