ArticleAIDS (London, England)2017
Multimodal analysis of drug transporter expression in gastrointestinal tissue.
Article in AIDS (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
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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
12 citing papers in PubMed, 12 citations in OpenAlex.
- Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species.Science translational medicine · 2019Trial
- Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.Clinical pharmacology and therapeutics · 2026Review
- Heterogeneous Antiretroviral Drug Exposure in Male and Female Genital Tract Tissues.The Journal of infectious diseases · 2025Article
- Antiretroviral drug exposure in lymph nodes is heterogeneous and drug dependent.Journal of the International AIDS Society · 2022Article
- Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, Reverse Transcriptase Simian-Human Immunodeficiency Virus RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates.Antimicrobial agents and chemotherapy · 2021Article
- Antiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and Humans.Antimicrobial agents and chemotherapy · 2020Article
- Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug-Drug Interaction Studies.Clinical pharmacokinetics · 2020Review
- Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis.Antimicrobial agents and chemotherapy · 2020Article
- Antiretroviral Penetration across Three Preclinical Animal Models and Humans in Eight Putative HIV Viral Reservoirs.Antimicrobial agents and chemotherapy · 2019Article
- Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- Antiretroviral Drug Concentrations in Lymph Nodes: A Cross-Species Comparison of the Effect of Drug Transporter Expression, Viral Infection, and Sex in Humanized Mice, Nonhuman Primates, and Humans.The Journal of pharmacology and experimental therapeutics · 2019Article
- Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms.The Journal of pharmacology and experimental therapeutics · 2018Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesDrug transporters affect antiretroviral therapy (ART) tissue disposition, but quantitative measures of drug transporter protein expression across preclinical species are not available. Our objective was to use proteomics to obtain absolute transporter concentrations and assess agreement with corresponding gene and immunometric protein data.
designIn order to make interspecies comparisons, two humanized mouse [hu-HSC-Rag (n = 41); bone marrow-liver-thymus (n = 13)] and one primate [rhesus macaque (nonhuman primate, n = 12)] models were dosed to steady state with combination ART. Ileum and rectum were collected at necropsy and snap frozen for analysis.
methodsTissues were analyzed for gene (quantitative PCR) and protein [liquid chromatography-mass spectrometry (LC-MS) proteomics and western blot] expression and localization (immunohistochemistry) of ART efflux and uptake transporters. Drug concentrations were measured by LC-MS/MS. Multivariable regression was used to determine the ability of transporter data to predict tissue ART penetration.
resultsAnalytical methods did not agree, with different trends observed for gene and protein expression. For example, quantitative PCR analysis showed a two-fold increase in permeability glycoprotein expression in nonhuman primates versus mice; however, proteomics showed a 200-fold difference in the opposite direction. Proteomics results were supported by immunohistochemistry staining showing extensive efflux transporter localization on the luminal surface of these tissues. ART tissue concentration was variable between species, and multivariable regression showed poor predictive power of transporter data.
conclusionLack of agreement between analytical techniques suggests that resources should be focused on generating downstream measures of protein expression to predict drug exposure. Taken together, these data inform the use of preclinical models for studying ART distribution and the design of targeted therapies for HIV eradication.
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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.