ArticleThe Journal of antimicrobial chemotherapy2015
Pharmacokinetic profile of raltegravir, elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir.Frontiers in cellular and infection microbiology · 2023Trial
- Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP).The Journal of antimicrobial chemotherapy · 2021Trial
- Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men.Journal of the International AIDS Society · 2018Trial
- Pharmacokinetics, the Immunological Impact, and the Effect on HIVAIDS research and human retroviruses · 2023Article
- Combination Antiretroviral Therapy and Immunophenotype of Feline Immunodeficiency Virus.Viruses · 2023Article
- Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men.The Journal of antimicrobial chemotherapy · 2023Article
- Article
- Endolysosome Localization of ERα Is Involved in the Protective Effect of 17α-Estradiol against HIV-1 gp120-Induced Neuronal Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Antiretroviral drug exposure in urethral and glans surface sampling of the penis.The Journal of antimicrobial chemotherapy · 2021Article
- Single oral dose for HIV pre or post-exposure prophylaxis: user desirability and biological efficacy in macaques.EBioMedicine · 2020Article
- Novel Transmitted/Founder Simian-Human Immunodeficiency Viruses for Human Immunodeficiency Virus Latency and Cure Research.Journal of virology · 2020Article
- Antiretroviral Penetration across Three Preclinical Animal Models and Humans in Eight Putative HIV Viral Reservoirs.Antimicrobial agents and chemotherapy · 2019Article
- Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1Antiviral research · 2018Article
- Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.Pharmaceutical research · 2017Article
- Multimodal analysis of drug transporter expression in gastrointestinal tissue.AIDS (London, England) · 2017Article
- Tenofovir alafenamide and elvitegravir loaded nanoparticles for long-acting prevention of HIV-1 vaginal transmission.AIDS (London, England) · 2017Article
- Article
- A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges.The Journal of antimicrobial chemotherapy · 2016Article
- Article
- Nonhuman Primates and Humanized Mice for Studies of HIV-1 Integrase Inhibitors: A Review.Pathogens & immunity · 2016Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesPharmacokinetic studies in animal models are important for assessing the prophylactic potential of antiretroviral drugs for HIV prevention. This study sought to identify clinically relevant doses of the marketed integrase inhibitors raltegravir, elvitegravir and dolutegravir in macaques and investigate drug penetration and antiviral activity in mucosal secretions.
methodsMacaques received one oral dose of raltegravir, elvitegravir or dolutegravir alone or in combination with emtricitabine and tenofovir disoproxil fumarate followed by drug level measurements in blood and rectal and vaginal secretions. Antiviral activity was investigated in TZM-bl cells exposed to SHIV162p3 in the presence of rectal secretions collected from treated animals.
resultsPlasma drug concentrations with 50 mg/kg raltegravir or elvitegravir were within the range seen in humans receiving 400-800 mg of raltegravir or 800 mg of unboosted elvitegravir but lower than with 150 mg of elvitegravir boosted with cobicistat. AUC0-24 values for dolutegravir increased proportionally with the dose, with a calculated human-equivalent dose of 20 mg/kg. Elvitegravir showed the highest penetration in rectal and vaginal fluids despite the absence of pharmacological boosting, followed by raltegravir and dolutegravir. Rectal secretions collected at 24 h from treated macaques blocked infection of TZM-bl cells by 50% at dilutions of 1/1000 (raltegravir), 1/800 (dolutegravir) and >1/30 000 (elvitegravir).
conclusionsWe defined macaque doses of HIV integrase inhibitors that recapitulate human clinical doses, which will facilitate efficacy and dose escalation studies in macaques. High and sustained drug concentrations and activity in mucosal secretions suggest that integrase inhibitors are promising candidates for HIV prevention.
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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.