ArticleJournal of acquired immune deficiency syndromes (1999)2012
Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, tenofovir.
Article in Journal of acquired immune deficiency syndromes (1999), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.CNS drugs · 2025Pooled it
- Trial
- Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.Journal of neurovirology · 2017Trial
- HIV expression persists in the cerebrospinal fluid of HIV-associated neurocognitive disorders despite effective ART.Emerging microbes & infections · 2026Article
- The case for targeting latent and lytic Epstein-Barr virus infection in multiple sclerosis.Brain : a journal of neurology · 2025Review
- Evaluation of Hippocampal Microanatomy and Neuro-Biomarkers Following Administration of Silver Nanoparticles Conjugated with Tenofovir Disoproxil Fumarate in Experimental Diabetic Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Postmortem Analysis of Dolutegravir, Tenofovir, Lamivudine, and Efavirenz Penetration in Multiple Central Nervous System Compartments.The Journal of infectious diseases · 2024Article
- Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation.The Journal of clinical investigation · 2024Article
- The central nervous system is a potential reservoir and possible origin of drug resistance in hepatitis B infection.Journal of virus eradication · 2023Article
- Morphine disrupts macrophage functions even during HIV infection.Journal of leukocyte biology · 2022Article
- Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis.Biomedicines · 2022Article
- BAGEL: A BAYESIAN GRAPHICAL MODEL FOR INFERRING DRUG EFFECT LONGITUDINALLY ON DEPRESSION IN PEOPLE WITH HIV.The annals of applied statistics · 2022Article
- T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.PLoS pathogens · 2021Article
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Associations between Antiretroviral Drugs on Depressive Symptomatology in Homogenous Subgroups of Women with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid.Southern African journal of HIV medicine · 2021Article
- Antiretroviral drug concentrations in brain tissue of adult decedents.AIDS (London, England) · 2020Article
- HIV-1 Sanctuary Sites-the Role of Membrane-Associated Drug Transporters and Drug Metabolic Enzymes.The AAPS journal · 2020Review
- Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders.Fluids and barriers of the CNS · 2020Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundTenofovir is a nucleotide HIV reverse transcriptase inhibitor whose chemical properties suggest that it may not penetrate into the central nervous system in therapeutic concentrations. The study's objective was to determine tenofovir's penetration into cerebrospinal fluid (CSF).
methodsCNS HIV Antiretroviral Therapy Effects Research is a multicenter observational study to determine the effects of antiretroviral therapy on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within an hour of each other from subjects taking tenofovir between October 2003 and March 2007. All samples were assayed by mass spectrometry with a detection limit of 0.9 ng/mL.
resultsOne hundred eighty-three participants (age 44 ± 8 years; 83 ± 32 kg; 33 females; CSF protein 44 ± 16 mg/dL) had plasma and CSF samples drawn 12.2 ± 6.9 and 11 ± 7.8 hours post dose, respectively. Median plasma and CSF tenofovir concentrations were 96 ng/mL [interquartile range (IQR) 47-153 ng/mL] and 5.5 ng/mL (IQR 2.7-11.3 ng/mL), respectively. Thirty-four of 231 plasma (14.7%) and 9 of 77 CSF samples (11.7%) were below detection. CSF to plasma concentration ratio from paired samples was 0.057 (IQR 0.03-0.1; n = 38). Median CSF to wild-type 50% inhibitory concentration ratio was 0.48 (IQR 0.24-0.98). Seventy-seven percent of CSF concentrations were below the tenofovir wild-type 50% inhibitory concentration. More subjects had detectable CSF HIV with lower (≤ 7 ng/mL) versus higher (>7 ng/mL) CSF tenofovir concentrations (29% versus 9%; P = 0.05).
conclusionsTenofovir concentrations in the CSF are only 5% of plasma concentrations, suggesting limited transfer into the CSF, and possibly active transport out of the CSF. CSF tenofovir concentrations may not effectively inhibit viral replication in the CSF.
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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.