ArticleThe Journal of antimicrobial chemotherapy2013
Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration.
Article in The Journal of antimicrobial chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed.
- 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
- Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.Journal of clinical pharmacology · 2014Trial
- Simultaneous pharmacokinetic modeling of unbound and total darunavir with ritonavir in adolescents: a substudy of the SMILE trial.Antimicrobial agents and chemotherapy · 2024Article
- Central nervous system disorders after use of dolutegravir: evidence from preclinical and clinical studies.Pharmacological reports : PR · 2023Review
- Luminescent PLGA Nanoparticles for Delivery of Darunavir to the Brain and Inhibition of Matrix Metalloproteinase-9, a Relevant Therapeutic Target of HIV-Associated Neurological Disorders.ACS chemical neuroscience · 2021Article
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection.AIDS (London, England) · 2020Article
- Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39).Journal of neurovirology · 2018Article
- Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain.Retrovirology · 2017Article
- Nanoformulated Antiretrovirals for Penetration of the Central Nervous System: State of the Art.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System.Current pharmaceutical design · 2016Review
- Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- Central nervous system penetration of antiretroviral drugs: pharmacokinetic, pharmacodynamic and pharmacogenomic considerations.Clinical pharmacokinetics · 2015Article
- Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.Current HIV/AIDS reports · 2015Review
- Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.Clinical pharmacokinetics · 2014Review
- Review
- HIV-1, HCV and alcohol in the CNS: potential interactions and effects on neuroinflammation.Current HIV research · 2014Review
- Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study.Journal of acquired immune deficiency syndromes (1999) · 2013Article
- Review
- Etravirine in CSF is highly protein bound.The Journal of antimicrobial chemotherapy · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
objectivesHigher CSF antiretroviral concentrations may be associated with better control of HIV replication and neurocognitive performance, but only the unbound fraction of antiretrovirals is available to inhibit HIV. Therefore, the objective of this study was to determine total and unbound darunavir concentrations in CSF and compare findings with plasma concentrations as well as the wild-type HIV-1 90% inhibitory concentration (IC(90)).
methodsSubjects with HIV infection were selected based on the use of darunavir-containing regimens with a twice-daily dosing schedule and availability of stored CSF and matched plasma. Total darunavir was measured by HPLC for plasma or liquid chromatography-tandem mass spectroscopy (LC/MS/MS) for CSF. Plasma unbound darunavir was measured by ultrafiltration and LC/MS/MS. CSF protein binding was determined by competitive binding exchange with radiolabelled darunavir.
resultsTwenty-nine matched CSF-plasma pairs were analysed and darunavir was detected in all CSF specimens (median total concentration 55.8 ng/mL), with a CSF unbound fraction of 93.5%. Median fractional penetrance was 1.4% of median total and 9.4% of median unbound plasma concentrations. Unbound darunavir concentrations in CSF exceeded the median IC(90) for wild-type HIV in all subjects by a median of 20.6-fold, despite the relatively low fractional penetrance. Total darunavir concentrations in CSF correlated with both total and unbound darunavir concentrations in plasma.
conclusionsDarunavir should contribute to the control of HIV replication in the CNS as a component of effective combination antiretroviral regimens.
Indexed as
Identifiers
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.