ArticleClinical pharmacokinetics2015
Central nervous system penetration of antiretroviral drugs: pharmacokinetic, pharmacodynamic and pharmacogenomic considerations.
Article in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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
41 citing papers in PubMed, 75 citations in OpenAlex.
- The Changing Spectrum of Cognitive Impairment in People with HIV; Establishment and Updates of the International HIV-Cognition Working Group.Current HIV/AIDS reports · 2026Review
- Efavirenz metabolism and CNS toxicity in Ugandan children: impact of CYP2B6 genotype and plasma metabolite profiles.Frontiers in pharmacology · 2026Article
- The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH.Viruses · 2025Review
- Cannabis use is associated with alterations in NLRP3 inflammasome related gene expression in monocyte-derived macrophages from people living with HIV.Frontiers in immunology · 2025Article
- Darunavir Nanoformulation Suppresses HIV Pathogenesis in Macrophages and Improves Drug Delivery to the Brain in Mice.Pharmaceutics · 2024Article
- HIV-1 Myeloid Reservoirs - Contributors to Viral Persistence and Pathogenesis.Current HIV/AIDS reports · 2024Review
- Deep analysis of CD4 T cells in the rhesus CNS during SIV infection.PLoS pathogens · 2023Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
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- Article
- Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients.Brain sciences · 2022Article
- Case study: New onset of neuropsychiatric symptoms following switching to a dolutegravir regimen.The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa · 2022Article
- Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection.Microorganisms · 2021Review
- Prolonged efavirenz exposure reduces peripheral oxytocin and vasopressin comparable to known drugs of addiction in male Sprague Dawley rats.IBRO neuroscience reports · 2021Article
- Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems.Pharmaceutics · 2021Review
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- PLGA Nanoparticle-Based Formulations to Cross the Blood-Brain Barrier for Drug Delivery: From R&D to cGMP.Pharmaceutics · 2021Review
- Evaluating Neurodevelopmental Consequences of Perinatal Exposure to Antiretroviral Drugs: Current Challenges and New Approaches.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- CNS Neurotoxicity of Antiretrovirals.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth.Frontiers in genetics · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevalence of HIV-associated neurocognitive disorder (HAND) is increasing despite the widespread use of combination antiretroviral therapy (ART). Initial reports suggest that the use of antiretrovirals with good central nervous system (CNS) penetration leads to better neurocognitive outcomes, but this has not yet been confirmed in a large cohort study or randomised controlled trial. There is emerging evidence that high CNS concentrations of some antiretrovirals are potentially neurotoxic and may be associated with the development of HAND. Antiretroviral CNS exposure is ideally determined by determining the ratio of cerebrospinal fluid (CSF):plasma area under the curve of unbound drug, but usually only total drug concentrations are measured and the ratio of CSF:plasma drug concentration is done at a single time point, which can result in misclassifying CNS penetration ability. Efavirenz was previously thought to have poor CNS penetration, measured by the CSF:plasma ratio (0.87%), but when unbound concentrations were measured it was found to have good CNS penetration (85%). Indinavir and efavirenz are the only antiretroviral drugs for which CNS area under the concentration-time curves using unbound plasma and CSF concentrations has been calculated. Patient data to support the contribution of blood-brain barrier transporter polymorphisms to CNS antiretroviral concentrations are currently limited and lack power to detect true associations. Correlations between CNS antiretroviral exposure and effect is multifaceted, and to accurately predict CNS effects there is a need to develop a sophisticated intra-brain pharmacokinetic-pharmacodynamic-pharmacogenetic model that includes transporters as well as the influence of HIV.
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What OpenQuestion holds
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.