Evidence map›Paper›PMID 38900910›Full record

ArticleThe Journal of infectious diseases2024

Postmortem Analysis of Dolutegravir, Tenofovir, Lamivudine, and Efavirenz Penetration in Multiple Central Nervous System Compartments.

Fan Wang, Kara Rademeyer, Olivie C Namuju, Kizito Abdusalaamu, James Fisher, David B Meya, MaryPeace McRae, David R Boulware, Robert Lukande, Melanie R Nicol

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Risk factors for cognitive decline in persons with HIV.Current opinion in infectious diseases · 2025
    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.

Fan WangDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Kara RademeyerDepartment of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, Virginia, USA.
Olivie C NamujuDepartment of Research, Infectious Diseases Institute, Kampala, Uganda.
Kizito AbdusalaamuDepartment of Pathology, Makerere University, Kampala, Uganda.
James FisherClinical Pharmacology Analytical Services, University of Minnesota, Minneapolis, Minnesota, USA.
David B MeyaDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-8854-0321
MaryPeace McRaeDepartment of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, Virginia, USA.
David R BoulwareDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-4715-0060
Robert LukandeDepartment of Pathology, Makerere University, Kampala, Uganda.
Melanie R NicolDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-5513-5509

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UM1TR004405 · NCATS · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar, Damien A Fair · 2023 to 2026
$30.8M
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Operational Research for Cryptococcal Antigen Screening (ORCAS) of HIV PatientsU01AI125003 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R, MEYA, DAVID BISAGAYA · 2016 to 2020
$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
Evaluating Antiretroviral Pharmacology in the Female Genital Tract to Optimize HIV PreventionK08AI134262 · NIAID · UNIVERSITY OF MINNESOTA · PI NICOL, MELANIE RAE · 2018 to 2022
$847k
Pharmacology of Antiretrovirals in Anatomical Brain Tissue among persons with chronic HIV infectionR21NS108344 · NINDS · UNIVERSITY OF MINNESOTA · PI LUKANDE, ROBERT, NICOL, MELANIE RAE · 2018 to 2019
$341k
National Institute of Allergy and Infectious Diseases K08AI134262National Institute of Neurologic Disorders and Stroke R21NS108344NCATS NIH HHS UM1 TR004405NIAID NIH HHS K08 AI134262NIAID NIH HHS U01 AI125003NIDA NIH HHS R01DA05315NIDA NIH HHS R01 DA053153NIH HHS 1UM1TR004405-01A1NINDS NIH HHS R01 NS086312NINDS NIH HHS R21 NS108344of MinnesotaUniversity
6 · The paper itself

Abstract

backgroundCentral nervous system (CNS) compartmentalization provides opportunity for human immunodeficiency virus (HIV) persistence and resistance development. Differences between cerebrospinal fluid (CSF) and cerebral matter regarding HIV persistence are well described. However, CSF is often used as surrogate for CNS drug exposure, and knowledge from solid brain tissue is rare.

methodsDolutegravir, tenofovir, lamivudine, and efavirenz concentrations were measured across 13 CNS regions plus plasma in samples collected during autopsy in 49 Ugandan decedents. Median time from death to autopsy was 8 hours (interquartile range, 5-15 hours). To evaluate postmortem redistribution, a time course study was performed in a mouse model.

resultsRegions with the highest penetration ratios were choroid plexus/arachnoid (dolutegravir and tenofovir), CSF (lamivudine), and cervical spinal cord/meninges (efavirenz); the lowest were corpus callosum (dolutegravir and tenofovir), frontal lobe (lamivudine), and parietal lobe (efavirenz). On average, brain concentrations were 84%, 87%, and 76% of CSF for dolutegravir, tenofovir, and lamivudine, respectively. Postmortem redistribution was observed in the mouse model, with tenofovir and lamivudine concentration increased by 350% and efavirenz concentration decreased by 24% at 24 hours postmortem.

conclusionsAnalysis of postmortem tissue provides a unique opportunity to investigate CNS antiretroviral penetration. Regional differences were observed paving the way to identify mechanisms of viral compartmentalization and/or neurotoxicity.

Indexed as

AlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesHeterocyclic Compounds, 3-RingHIV InfectionsLamivudineOxazinesPiperazinesPyridonesTenofovirAdultAnimalsAutopsyBrainCentral Nervous SystemAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesDolutegravirefavirenzHeterocyclic Compounds, 3-RingLamivudineOxazinesPiperazinesPyridonesTenofovirantiretroviralcentral nervous systemHIVpenetrationpostmortem analysis

Identifiers

PMID38900910
PMCPMC11565900

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.