Cerebrospinal fluid concentrations of tenofovir and emtricitabine in the setting of HIV‐1 protease inhibitor‐based regimens

Lahiri, Cecile D.; Reed-Walker, Kedria; Sheth, Anandi N.; Acosta, Edward P.; Vunnava, Aswani; Ofotokun, Ighovwerha

doi:10.1002/jcph.612

Cited by 20 publications

(18 citation statements)

References 20 publications

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“…To our knowledge, this is the first study to report CNS exposure of TFV from an oral administration of TAF (10 mg) with the combination of elvitegravir, cobicistat, and emtricitabine. This study reports similar TFV concentrations in CSF after TDF (300 mg) oral administration [17, 18]. The comparative results of this study further prove the accuracy and usefulness of the LC-MS/MS assay that was developed and validated.…”

Section: Resultssupporting

confidence: 65%

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Development and validation of an LC–MS/MS assay for tenofovir and tenofovir alafenamide in human plasma and cerebrospinal fluid

Ocque

Hagler

Morse

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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A liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of tenofovir and tenofovir alafenamide concentrations in human plasma and cerebrospinal fluid. Tenofovir and tenofovir alafenamide were extracted from matrix by solid phase extraction. The dried extraction eluents were dissolved in water for LC-MS/MS analysis. Separation was achieved with a Phenomenex Synergi 4 μm Polar-RP 80A column (50 × 2 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 5 min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 500 ng/mL for the plasma assay and 0.1-50 ng/mL for the cerebrospinal fluid assay. The intra- and inter-day accuracy and precision were less than 12% in low, medium, and high quality control samples for both matrices. The validated methods were applied to the analysis of plasma and cerebrospinal fluid samples of a patient undergoing tenofovir therapy which involved the switch from Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg).

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Section: Resultssupporting

confidence: 65%

“…Several analytical assays have been published for the determination of TFV concentration in human plasma [11–16] while few have discussed the measurement of TFV in CSF [17, 18]. TAF has been measured in human plasma [19, 20] with little method description or assay validation metrics described.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an LC–MS/MS assay for tenofovir and tenofovir alafenamide in human plasma and cerebrospinal fluid

Ocque

Hagler

Morse

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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“…Polyethyleneimines (PEIs) are positively charged polymers used to deliver siRNAs for the induction of RNA interference (RNAi) and to mediate their endosomal release [ 32 ]. Since myeloid (macrophages and microglia) and astrocytes express mannose receptors [ 33 , 34 ], we used a mannose-bearing PEI as a homing ligand for the specific and selective recognition of brain cells expressing the mannose receptor. Human microglia, human astrocytes, and human neuronal cell cultures were individually transfected with FITC-labeled control siRNA using a mannose (Man)-conjugated PEI reagent.…”

Section: Resultsmentioning

confidence: 99%

Targeting Beclin1 as an Adjunctive Therapy against HIV Using Mannosylated Polyethylenimine Nanoparticles

et al. 2021

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Using nanoparticle-based RNA interference (RNAi), we have previously shown that silencing the host autophagic protein, Beclin1, in HIV-infected human microglia and astrocytes restricts HIV replication and its viral-associated inflammatory responses. Here, we confirmed the efficacy of Beclin1 small interfering RNA (siBeclin1) as an adjunctive antiviral and anti-inflammatory therapy in myeloid human microglia and primary human astrocytes infected with HIV, both with and without exposure to combined antiretroviral (cART) drugs. To specifically target human microglia and human astrocytes, we used a nanoparticle (NP) comprised of linear cationic polyethylenimine (PEI) conjugated with mannose (Man) and encapsulated with siBeclin1. The target specificity of the PEI-Man NP was confirmed in vitro using human neuronal and glial cells transfected with the NP encapsulated with fluorescein isothiocyanate (FITC). PEI-Man-siBeclin1 NPs were intranasally delivered to healthy C57BL/6 mice in order to report the biodistribution of siBeclin1 in different areas of the brain, measured using stem-loop RT-PCR. Postmortem brains recovered at 1–48 h post-treatment with the PEI-Man-siRNA NP showed no significant changes in the secretion of the chemokines regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) and showed significant decreases in the secretion of the cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) when compared to phosphate-buffered saline (PBS)-treated brains. Nissl staining showed minimal differences between the neuronal structures when compared to PBS-treated brains, which correlated with no adverse behavioral affects. To confirm the brain and peripheral organ distribution of PEI-siBeclin1 in living mice, we used the In vivo Imaging System (IVIS) and demonstrated a significant brain accumulation of siBeclin1 through intranasal administration.

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“…In studies of adults with HIV, HIV-associated neurocognitive disorders (HAND) is attributed to poor control of HIV in the central nervous system, with limited CNS penetration by ARV drugs in cerebrospinal fluid associated with HAND 29,30 . A recent analysis of ARV drug concentrations in brain tissue collected from adults dying with HIV disease found that tenofovir, unlike other evaluated drugs, had higher concentrations than expected from previous levels found in cerebrospinal fluid 31 .…”

Section: Discussionmentioning

confidence: 99%

Risk for Speech and Language Impairments in Preschool Age HIV-exposed Uninfected Children With In Utero Combination Antiretroviral Exposure

Rice

Frederick

Purswani

et al. 2018

Pediatric Infectious Disease Journal

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Cerebrospinal fluid concentrations of tenofovir and emtricitabine in the setting of HIV‐1 protease inhibitor‐based regimens

Cited by 20 publications

References 20 publications

Development and validation of an LC–MS/MS assay for tenofovir and tenofovir alafenamide in human plasma and cerebrospinal fluid

Development and validation of an LC–MS/MS assay for tenofovir and tenofovir alafenamide in human plasma and cerebrospinal fluid

Targeting Beclin1 as an Adjunctive Therapy against HIV Using Mannosylated Polyethylenimine Nanoparticles

Risk for Speech and Language Impairments in Preschool Age HIV-exposed Uninfected Children With In Utero Combination Antiretroviral Exposure

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