ArticleJournal of virology2011
Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 75 citations in OpenAlex.
- 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
- Levels of Intracellular Phosphorylated Tenofovir and Emtricitabine Correlate With Natural Substrate Concentrations in Peripheral Blood Mononuclear Cells of Persons Prescribed Daily Oral Truvada for HIV Pre-exposure Prophylaxis.Journal of acquired immune deficiency syndromes (1999) · 2017Trial
- Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues.The Journal of antimicrobial chemotherapy · 2017Trial
- A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.The Journal of infectious diseases · 2016Trial
- PrEP at the site of action in cisgender and transgender women: A pharmacology study of blood and rectal CD4British journal of clinical pharmacology · 2026Article
- Prevotella bivia Influences Antiretroviral Pharmacokinetics and Viral Replication in an Ex Vivo Vaginal Tissue Model.Clinical and translational science · 2026Article
- SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity.Nature communications · 2024Article
- Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.Pharmaceutics · 2024Article
- Article
- Preclinical Considerations for Long-acting Delivery of Tenofovir Alafenamide from Subdermal Implants for HIV Pre-exposure Prophylaxis.Pharmaceutical research · 2023Article
- Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen.Microorganisms · 2023Article
- Translational Models to Predict Target Concentrations for Pre-Exposure Prophylaxis in Women.AIDS research and human retroviruses · 2022Review
- Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model.The Journal of antimicrobial chemotherapy · 2022Article
- Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- The predictive value of macaque models of preexposure prophylaxis for HIV prevention.Current opinion in HIV and AIDS · 2022Review
- Intracellular islatravir pharmacology differs between species in an in vitro model: implications for preclinical study design.The Journal of antimicrobial chemotherapy · 2022Article
- Tenofovir Alafenamide for HIV Prevention: Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting.AIDS research and human retroviruses · 2021Review
- Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates.Advanced therapeutics · 2021Article
- The effect of depot medroxyprogesterone acetate on tenofovir alafenamide in rhesus macaques.Antiviral research · 2021Article
- The Lymphoid Tissue Pharmacokinetics of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide in HIV-Infected Persons.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preexposure prophylaxis (PrEP) with antiretroviral drugs is a novel human immunodeficiency virus (HIV) prevention strategy. It is generally thought that high systemic and mucosal drug levels are sufficient for protection. We investigated whether GS7340, a next-generation tenofovir (TFV) prodrug that effectively delivers tenofovir diphosphate (TFV-DP) to lymphoid cells and tissues, could protect macaques against repeated weekly rectal simian-human immunodeficiency virus (SHIV) exposures. Macaques received prophylactic GS7340 treatment 3 days prior to each virus exposure. At 3 days postdosing, TFV-DP concentrations in peripheral blood mononuclear cells (PBMCs) were about 50-fold higher than those seen with TFV disoproxil fumarate (TDF), and they remained above 1,000 fmol/10(6) cells for as long as 7 days. TFV-DP accumulated in lymphoid and rectal tissues, with concentrations at 3 days exceeding 500 fmol/10(6) mononuclear cells. Despite high mucosal and systemic TFV levels, GS7340 was not protective. Since TFV-DP blocks reverse transcription by competing with the natural dATP substrate, we measured dATP contents in peripheral lymphocytes, lymphoid tissue, and rectal mononuclear cells. Compared to those in circulating lymphocytes and lymphoid tissue, rectal lymphocytes had 100-fold higher dATP concentrations and dATP/TFV-DP ratios, likely reflecting the activated status of the cells and suggesting that TFV-DP may be less active at the rectal mucosa. Our results identify dATP/TFV-DP ratios as a possible correlate of protection by TFV and suggest that natural substrate concentrations at the mucosa will likely modulate the prophylactic efficacy of nucleotide reverse transcriptase inhibitors.
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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.