ArticleAntimicrobial agents and chemotherapy2022
Islatravir Has a High Barrier to Resistance and Exhibits a Differentiated Resistance Profile from Approved Nucleoside Reverse Transcriptase Inhibitors (NRTIs).
Article in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 41 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
- Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 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
- Article
- 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
- Contemporary antiretroviral pharmacology in the male genital tract: implications for HIV treatment and prevention.Antimicrobial agents and chemotherapy · 2026Review
- Evaluation of Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet of Islatravir and Lenacapavir.Journal of clinical pharmacology · 2026Article
- Exploration of 4'-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents.Bioorganic & medicinal chemistry · 2025Article
- 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
- Nonclinical and clinical characterization of the absorption, metabolism, and excretion of islatravir.Antimicrobial agents and chemotherapy · 2025Article
- Article
- Article
- Comprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.Antiviral research · 2024Article
- 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
- Intracellular islatravir-triphosphate half-life supports extended dosing intervals.Antimicrobial agents and chemotherapy · 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
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits human immunodeficiency virus (HIV) reverse transcription by blocking reverse transcriptase (RT) translocation on the primer:template. ISL is being developed for the treatment of HIV-1 infection. To expand our knowledge of viral variants that may confer reduced susceptibility to ISL, resistance selection studies were conducted with wild-type (WT) subtype A, B, and C viruses. RT mutations encoding M184I and M184V were the most frequently observed changes. Selection studies were also initiated with virus containing a single known resistance-associated mutation in RT (K65R, L74I, V90I, M184I, or M184V), and no additional mutations were observed. Antiviral activity assays were performed on variants that emerged in selection studies to determine their impact. M184I and M184V were the only single-codon substitutions that reduced susceptibility >2-fold compared to WT. A114S was an emergent substitution that when combined with other substitutions further reduced susceptibility >2-fold. Viruses containing A114S in combination with M184V did not replicate in primary blood mononuclear cells (PBMCs), consistent with the rare occurrence of the combination in clinical samples. While A114S conferred reduced susceptibility to ISL, it increased susceptibility to approved nucleoside reverse transcriptase inhibitors (NRTIs). This differential impact of A114S on ISL, an NRTTI, compared to NRTIs likely results from the different mechanisms of action. Altogether, the results demonstrate that ISL has a high barrier to resistance and a differentiated mechanism compared to approved NRTIs.
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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.