ArticleAIDS (London, England)2020
Antiretroviral drug concentrations in brain tissue of adult decedents.
Article in AIDS (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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.
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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Mitochondrial changes associated with viral infectious diseases in the paediatric population.Reviews in medical virology · 2021Pooled it
- Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Evaluating "brain permeability": A critical issue for the development of therapeutic agents for primary and metastatic brain tumors.Neuro-oncology · 2026Review
- Smoldering in the sanctuary: HIV-associated brain injury in the ART era.The Journal of clinical investigation · 2026Review
- Exposure to Frontline Antiretroviral Dolutegravir Disrupts Oligodendrocyte Development Across Differentiation Stages.ASN neuro · 2026Article
- Article
- Article
- Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid.Pharmacotherapy · 2025Article
- Extracellular Vesicle-Liposome-Darunavir Formulation for the Treatment of HIV Neuropathogenesis.ACS applied nano materials · 2025Article
- HIV Cerebrospinal Fluid Escape: Interventions for the Management, Current Evidence and Future Perspectives.Tropical medicine and infectious disease · 2025Review
- Postmortem Analysis of Dolutegravir, Tenofovir, Lamivudine, and Efavirenz Penetration in Multiple Central Nervous System Compartments.The Journal of infectious diseases · 2024Article
- All Blood Brain Barrier Cell Types Demonstrate Capability to Influence Differential Tenofovir and Emtricitabine Metabolism and Transport in the Brain.ACS pharmacology & translational science · 2024Article
- Drug Metabolism and Transport Capacity of Endothelial Cells, Pericytes, and Astrocytes: Implications for CNS Drug Disposition.bioRxiv : the preprint server for biology · 2024Article
- HIV-1 Myeloid Reservoirs - Contributors to Viral Persistence and Pathogenesis.Current HIV/AIDS reports · 2024Review
- Tenofovir Activation Is Diminished in the Brain and Liver of Creatine Kinase Brain-Type Knockout Mice.ACS pharmacology & translational science · 2024Article
- Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier.Fluids and barriers of the CNS · 2024Article
- Differences in drug resistance of HIV-1 genotypes in CSF and plasma and analysis of related factors.Virulence · 2023Article
- GP120 and tenofovir alafenamide alter cannabinoid receptor 1 expression in hippocampus of mice.Journal of neurovirology · 2023Article
- Regional Analysis of Intact and Defective HIV Proviruses in the Brain of Viremic and Virally Suppressed People with HIV.Annals of neurology · 2023Article
- Tenofovir Activation is Diminished in the Brain and Liver of Creatine Kinase Brain-Type Knockout Mice.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveDetermine concentrations of antiretroviral therapy (ART) drugs in the human brain.
designCohort study of persons with HIV who consented to antemortem assessment and postmortem autopsy.
methodsEleven persons with HIV who were taking ART at the time of death and had detectable concentrations of at least one ART drug in intracardiac aspirate at autopsy were evaluated. Autopsies were performed within 24 h of death and brain tissue was stored at -80 °C. Concentrations of 11 ART drugs were measured in three brain regions (globus pallidus, cortical gray matter, white matter) by HPLC tandem mass spectrometry with a lower limit of quantification of 25 ng/ml.
resultsParticipants were mostly men (82%) with a mean age of 40.4 years. Drug concentrations in brain tissue were highly variable and exceeded published concentrations in cerebrospinal fluid for several drugs, including for tenofovir, efavirenz, and lopinavir. Drug concentrations correlated most strongly between cortical gray matter and globus pallidus (rho = 0.70) but less well between globus pallidus and white matter (rho = 0.43). Combining all drugs and brain regions (n = 89), higher drug concentrations in brain were associated with longer estimated duration of HIV infection (P = 0.015), lower HIV RNA in plasma (P = 0.0001), lower nadir CD4 T-cell count (P = 0.053), and worse neurocognitive performance (P = 0.017).
conclusionThis is the first analysis of ART drug concentrations in human brain tissue. Concentrations of several drugs in this analysis were similar to published concentrations in cerebrospinal fluid but others exceeded published concentrations. The association between higher drug concentrations in the brain and worse neurocognitive performance may indicate ART neurotoxicity.
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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.