Evidence map›Paper›PMID 31102185›Full record

ArticleJournal of neurovirology2019

HIV-1 Tat and opioids act independently to limit antiretroviral brain concentrations and reduce blood-brain barrier integrity.

Crystal R Leibrand, Jason J Paris, Austin M Jones, Quamrun N Masuda, Matthew S Halquist, Woong-Ki Kim, Pamela E Knapp, Angela D M Kashuba, Kurt F Hauser, MaryPeace McRae

Open access · greenAbstract read
In one paragraph

Article in Journal of neurovirology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 34 citations in OpenAlex.

  1. Enhancing the Sensitivity of Mass Spectrometry Imaging through Spatial Signal Averaging.Journal of the American Society for Mass Spectrometry · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Expression of Human Immunodeficiency Virus Transactivator of Transcription (HIV-TatJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Effect of Opioid Use on Immune Activation and HIV Persistence on ART.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Crystal R LeibrandDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Jason J ParisDepartment of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
Austin M JonesDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Quamrun N MasudaDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Matthew S HalquistDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Woong-Ki KimDepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, 23507, USA.
Pamela E KnappDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Angela D M KashubaDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7569, USA.
Kurt F HauserDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
MaryPeace McRaeDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA. mpmcrae@vcu.edu.ORCID 0000-0003-1408-0868
Virginia Commonwealth University · USEastern Virginia Medical School · USUniversity of Mississippi · USUniversity of North Carolina at Chapel Hill · US

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Research Supplement to Promote Diversity in Health Related ResearchUL1TR002649 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2018 to 2022
$19.1M
Center for Clinical and Translational ResearchUL1TR000058 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2012 to 2015
$12.5M
MOR and CCR5 interactive signaling mediates opiate and HIV-driven synaptodendritic injuryR01DA034231 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F, KNAPP, PAMELA E · 2013 to 2023
$5.4M
Mechanisms of Opiate Drug-HIV-Induced NeurodegenerationR01DA018633 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F · 2005 to 2021
$4.4M
Translational Research in Neuro-AIDS and Mental HealthR25MH080661 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MCARTHUR, JUSTIN CHARLES. · 2007 to 2019
$2.9M
HIV opiate interactions in white matter pathologyR01DA044939 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F, KNAPP, PAMELA E · 2017 to 2021
$2.7M
Bivalent Ligands as Chemical Probes to Study Opioid Abuse-enhanced HIV InfectionR01DA044855 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F, ZHANG, YAN · 2017 to 2021
$2.7M
Regulation of HIV and opiate-directed synaptodendritic injury/death in striatumR01DA033200 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F · 2013 to 2017
$2.1M
Selective vulnerability of discrete neural circuits in the striatum to HIV-opiate comorbidityR01DA045588 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F · 2018 to 2022
$2.0M
Neuron-Glia Mechanisms & Interactions Underlying Opioid Abuse-HIV-1 ComorbidityK02DA027374 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F · 2009 to 2018
$1.3M
Opiate abuse and sex steroids influence neuroAIDS pathologyR00DA039791 · NIDA · UNIVERSITY OF MISSISSIPPI · PI PARIS, JASON RICHARD · 2017 to 2019
$734k
NCATS NIH HHS UL1 TR000058NCATS NIH HHS UL1 TR002649NIAID NIH HHS P30 AI050410NIDA NIH HHS K02 DA027374NIDA NIH HHS R00 DA039791NIDA NIH HHS R01 DA018633NIDA NIH HHS R01 DA033200NIDA NIH HHS R01 DA034231NIDA NIH HHS R01 DA044855NIDA NIH HHS R01 DA044939NIDA NIH HHS R01 DA045588NIDA NIH HHS R21 DA045630NIMH NIH HHS R25 MH080661
6 · The paper itself

Abstract

Poor antiretroviral penetration may contribute to human immunodeficiency virus (HIV) persistence within the brain and to neurocognitive deficits in opiate abusers. To investigate this problem, HIV-1 Tat protein and morphine effects on blood-brain barrier (BBB) permeability and drug brain penetration were explored using a conditional HIV-1 Tat transgenic mouse model. Tat and morphine effects on the leakage of fluorescently labeled dextrans (10-, 40-, and 70-kDa) into the brain were assessed. To evaluate effects on antiretroviral brain penetration, Tat+ and Tat- mice received three antiretroviral drugs (dolutegravir, abacavir, and lamivudine) with or without concurrent morphine exposure. Antiretroviral and morphine brain and plasma concentrations were determined by LC-MS/MS. Morphine exposure, and, to a lesser extent, Tat, significantly increased tracer leakage from the vasculature into the brain. Despite enhanced BBB breakdown evidenced by increased tracer leakiness, morphine exposure led to significantly lower abacavir concentrations within the striatum and significantly less dolutegravir within the hippocampus and striatum (normalized to plasma). P-glycoprotein, an efflux transporter for which these drugs are substrates, expression and function were significantly increased in the brains of morphine-exposed mice compared to mice not exposed to morphine. These findings were consistent with lower antiretroviral concentrations in brain tissues examined. Lamivudine concentrations were unaffected by Tat or morphine exposure. Collectively, our investigations indicate that Tat and morphine differentially alter BBB integrity. Morphine decreased brain concentrations of specific antiretroviral drugs, perhaps via increased expression of the drug efflux transporter, P-glycoprotein.

Indexed as

AbacavirAnimalsAnti-HIV AgentsATP Binding Cassette Transporter, Subfamily B, Member 1Biological TransportBlood-Brain BarrierCapillary PermeabilityCorpus StriatumDextransDideoxynucleosidesDolutegravirFemaleFluorescein-5-isothiocyanateHeterocyclic Compounds, 3-RingHippocampusHIV-1AbacavirAnti-HIV AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DextransDideoxynucleosidesDolutegravirFluorescein-5-isothiocyanatefluorescein isothiocyanate dextranHeterocyclic Compounds, 3-RingLamivudineMorphineOxazinesPiperazinesPyridonestat Gene Products, Human Immunodeficiency VirusAbacavirDolutegravirLamivudineMorphine-3-β-glucuronideNeuro-human immunodeficiency virus (neuroHIV)Paracellular transportP-glycoproteinTranscellular transportZonula occludens-1

Identifiers

PMID31102185
PMCPMC6750988
OpenAlexW2945479002

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.