ArticleThe Journal of biological chemistry2014
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 111 citations in OpenAlex.
- Islatravir distribution in plasma, peripheral blood mononuclear cells, and mucosal tissues after monthly oral dosing.AIDS (London, England) · 2026Trial
- Population pharmacokinetics of tenofovir alafenamide delivered via an annual subdermal implant in South African women.Scientific reports · 2026Trial
- Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1: results from a randomized trial.AIDS (London, England) · 2026Trial
- Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.Antimicrobial agents and chemotherapy · 2024Trial
- 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.Antimicrobial agents and chemotherapy · 2021Trial
- Safety and pharmacokinetics of islatravir subdermal implant for HIV-1 pre-exposure prophylaxis: a randomized, placebo-controlled phase 1 trial.Nature medicine · 2021Trial
- Safety, tolerability, and pharmacokinetics of single- and multiple-dose administration of islatravir (MK-8591) in adults without HIV.Clinical and translational science · 2021Trial
- Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.bioRxiv : the preprint server for biology · 2026Article
- Article
- Unraveling the Mechanism of HIV-1 Hypersusceptibility to Tenofovir Imparted by Islatravir Resistance Mutations.bioRxiv : the preprint server for biology · 2026Article
- Structural Basis of Polypurine Track Strand Displacement by HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing.PLoS biology · 2025Article
- Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine.NAR molecular medicine · 2025Article
- Pharmacokinetics of Atorvastatin and Metformin after Coadministration with Islatravir in Healthy Adults.Journal of clinical pharmacology · 2025Article
- Pharmacokinetics of islatravir in participants with moderate hepatic impairment.Antimicrobial agents and chemotherapy · 2025Article
- Nonclinical and clinical characterization of the absorption, metabolism, and excretion of islatravir.Antimicrobial agents and chemotherapy · 2025Article
- Article
- A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.Clinical pharmacology in drug development · 2025Article
- State of the ART (antiretroviral therapy): Long-acting HIV-1 therapeutics.Global health & medicine · 2024Review
- Modeling of HIV-1 prophylactic efficacy and toxicity with islatravir shows non-superiority for oral dosing, but promise as a subcutaneous implant.CPT: pharmacometrics & systems pharmacology · 2024Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside analog that, unlike approved anti-human immunodeficiency virus type 1 (HIV-1) nucleoside reverse transcriptase inhibitors, has a 3'-OH and exhibits remarkable potency against wild-type and drug-resistant HIVs. EFdA triphosphate (EFdA-TP) is unique among nucleoside reverse transcriptase inhibitors because it inhibits HIV-1 reverse transcriptase (RT) with multiple mechanisms. (a) EFdA-TP can block RT as a translocation-defective RT inhibitor that dramatically slows DNA synthesis, acting as a de facto immediate chain terminator. Although non-translocated EFdA-MP-terminated primers can be unblocked, they can be efficiently converted back to the EFdA-MP-terminated form. (b) EFdA-TP can function as a delayed chain terminator, allowing incorporation of an additional dNTP before blocking DNA synthesis. In such cases, EFdA-MP-terminated primers are protected from excision. (c) EFdA-MP can be efficiently misincorporated by RT, leading to mismatched primers that are extremely hard to extend and are also protected from excision. The context of template sequence defines the relative contribution of each mechanism and affects the affinity of EFdA-MP for potential incorporation sites, explaining in part the lack of antagonism between EFdA and tenofovir. Changes in the type of nucleotide before EFdA-MP incorporation can alter its mechanism of inhibition from delayed chain terminator to immediate chain terminator. The versatility of EFdA in inhibiting HIV replication by multiple mechanisms may explain why resistance to EFdA is more difficult to emerge.
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Registered trials
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.