Trial reportJournal of clinical pharmacology2014
Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.
Trial report in Journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 21 citations in OpenAlex.
- Trial
- Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid.Pharmacotherapy · 2025Article
- Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation.The Journal of clinical investigation · 2024Article
- Machine learning methods for developments of binding kinetic models in predicting protein-ligand dissociation rate constants.Smart molecules : open access · 2023Article
- Central nervous system disorders after use of dolutegravir: evidence from preclinical and clinical studies.Pharmacological reports : PR · 2023Review
- Pharmacologic approaches to HIV-associated neurocognitive disorders.Current opinion in pharmacology · 2020Review
- In Silico Prediction of the Dissociation Rate Constants of Small Chemical Ligands by 3D-Grid-Based VolSurf Method.International journal of molecular sciences · 2020Article
- Mechanistic framework predicts drug-class specific utility of antiretrovirals for HIV prophylaxis.PLoS computational biology · 2019Article
- Evaluation of cerebrospinal fluid virological escape in patients on long-term protease inhibitor monotherapy.Antiviral therapy · 2017Article
- Cerebrospinal fluid concentrations of tenofovir and emtricitabine in the setting of HIV-1 protease inhibitor-based regimens.Journal of clinical pharmacology · 2016Article
- Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals.AIDS research and treatment · 2016Review
- Impact of protease inhibitors on intracellular concentration of tenofovir-diphosphate among HIV-1 infected patients.AIDS (London, England) · 2015Article
- Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.Clinical pharmacokinetics · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06-0.12] than DRV, 0.04 (95%CI 0.03-0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50 ) in all ATV and 1 DRV-treated subjects (P < 0.001). CSF HIV-1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV-1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation.
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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.