ArticleThe Journal of antimicrobial chemotherapy2011
Efavirenz concentrations in CSF exceed IC50 for wild-type HIV.
Article in The Journal of antimicrobial chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 91 citations in OpenAlex.
- Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults.The Journal of antimicrobial chemotherapy · 2020Trial
- Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.PLoS pathogens · 2016Trial
- ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- A novel measure of antiretroviral activity in cerebrospinal fluid and association with HIV persistence and cognitive function.AIDS (London, England) · 2026Article
- A nanopore-based HIV-1 reference epitranscriptome.Nucleic acids research · 2026Article
- 7,8-Dihydroxy Efavirenz Is Not as Effective in CYP46A1 Activation In Vivo as Efavirenz or Its 8,14-Dihydroxy Metabolite.International journal of molecular sciences · 2024Article
- Central nervous system disorders after use of dolutegravir: evidence from preclinical and clinical studies.Pharmacological reports : PR · 2023Review
- Biotransformation of Efavirenz and Proteomic Analysis of Cytochrome P450s and UDP-Glucuronosyltransferases in Mouse, Macaque, and Human Brain-Derived In Vitro Systems.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- The Hydroxylation Position Rather than Chirality Determines How Efavirenz Metabolites Activate Cytochrome P450 46A1 In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- The capacity of HIV in the blood and the cerebrospinal fluid depending on antiretroviral drugs.Journal of medicine and life · 2022Article
- Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages.Antimicrobial agents and chemotherapy · 2022Article
- Intramuscular and subcutaneous administration of antiretroviral drugs, compared with oral, enhances delivery to lymphoid tissues in BALB/c mice.The Journal of antimicrobial chemotherapy · 2021Article
- T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.PLoS pathogens · 2021Article
- Review
- Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells.Frontiers in immunology · 2021Article
- Antiretroviral drug concentrations in brain tissue of adult decedents.AIDS (London, England) · 2020Article
- In Vitro Activation of Cytochrome P450 46A1 (CYP46A1) by Efavirenz-Related Compounds.Journal of medicinal chemistry · 2020Article
- Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma.EMBO molecular medicine · 2020Article
- Antiretroviral Penetration across Three Preclinical Animal Models and Humans in Eight Putative HIV Viral Reservoirs.Antimicrobial agents and chemotherapy · 2019Article
- Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs.ACS omega · 2019Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
objectivesHIV-associated neurocognitive disorders remain common despite use of potent antiretroviral therapy (ART). Ongoing viral replication due to poor distribution of antivirals into the CNS may increase risk for HIV-associated neurocognitive disorders. This study's objective was to determine penetration of a commonly prescribed antiretroviral drug, efavirenz, into CSF.
methodsCHARTER is an ongoing, North American, multicentre, observational study to determine the effects of ART on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within 1 h of each other from subjects taking efavirenz between September 2003 and July 2007. Samples were assayed by HPLC or HPLC/mass spectrometry with detection limits of 39 ng/mL (plasma) and <0.1 ng/mL (CSF).
resultsEighty participants (age 44 ± 8 years; 79 ± 15 kg; 20 females) had samples drawn 12.5 ± 5.4 h post-dose. The median efavirenz concentrations after a median of 7 months [interquartile range (IQR) 2-17] of therapy were 2145 ng/mL in plasma (IQR 1384-4423) and 13.9 ng/mL in CSF (IQR 4.1-21.2). The CSF/plasma concentration ratio from paired samples drawn within 1 h of each other was 0.005 (IQR 0.0026-0.0076; n = 69). The CSF/IC(50) ratio was 26 (IQR 8-41) using the published IC(50) for wild-type HIV (0.51 ng/mL). Two CSF samples had concentrations below the efavirenz IC(50) for wild-type HIV.
conclusionsEfavirenz concentrations in the CSF are only 0.5% of plasma concentrations but exceed the wild-type IC(50) in nearly all individuals. Since CSF drug concentrations reflect those in brain interstitial fluids, efavirenz reaches therapeutic concentrations in brain tissue.
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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.