Evidence map›Paper›PMID 39382215›Full record

ArticleClinical and translational science2024

Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Austin M Jones, Kara M Rademeyer, Elias P Rosen, Silas Contaifer, Dayanjan Wijesinghe, Kurt F Hauser, MaryPeace McRae

Abstract read
In one paragraph

Article in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  2. Article
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

7 authors.

Austin M JonesDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID 0000-0001-8043-1115
Kara M RademeyerDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.
Elias P RosenDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Silas ContaiferDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID 0000-0002-1091-8144
Dayanjan WijesingheDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.
Kurt F HauserDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID 0000-0001-7886-0332
MaryPeace McRaeDepartment of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID 0000-0003-1408-0868

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Innovative therapeutic approaches to address excitotoxic CNS/neuronal damage in opioid-neuroHIV comorbidityR01DA057346 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kurt F Hauser, Pamela E Knapp · 2022 to 2026
$3.4M
Opioid- and HIV-mediated effects on the integrity of the blood-brain barrier, on immune cell recruitment, and on antiretroviral penetration into thebrainR01DA053153 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MCRAE, MARY PEACE · 2021 to 2025
$2.5M
NIAID NIH HHS P30 AI050410NIDA NIH HHS R01 DA053153NIH HHS P30AI050410 (UNC Center for AIDS Research)NIH HHS R01DA053153NIH HHS R01DA057346
6 · The paper itself

Abstract

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI). Morphine exposure uniquely decreased antiretroviral concentrations in anterior cerebral (primary motor and somatosensory) cortices, corpus collosum (anterior forceps), caudoputamen, nucleus accumbens, and posterior regions including the hippocampus, corpus callosum (main body), cerebral cortex (somatosensory and auditory cortices), thalamus, and hypothalamus. Interestingly, male mice experienced greater morphine-associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in antiretroviral concentrations were linked with inflammation in astroglia, assessed through the measurement of astroglial activation using glial fibrillary acidic protein (GFAP) as a marker. Alterations in antiretroviral concentrations co-registering with areas of astroglial activation exhibited sex-specific treatment differences. This study highlights the intricate interplay between HIV, opioids, and antiretroviral drugs within the CNS, elucidating distinct regional and sex variations in responsiveness. Our findings emphasize the identification of vulnerabilities within the neural landscape and underscore the necessity of carefully monitoring opioid use to maintain the efficacy of antiretroviral therapies.

Indexed as

BrainHIV-1Morphinetat Gene Products, Human Immunodeficiency VirusAnalgesics, OpioidAnimalsAnti-Retroviral AgentsDisease Models, AnimalFemaleGlial Fibrillary Acidic ProteinHIV InfectionsHumansMaleMiceMice, TransgenicAnalgesics, OpioidAnti-Retroviral AgentsGlial Fibrillary Acidic ProteinMorphinetat Gene Products, Human Immunodeficiency Virus

Identifiers

PMID39382215
PMCPMC11462598

What OpenQuestion holds

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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.