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Darunavir concentrations in CSF of HIV-infected individuals when boosted with cobicistat versus ritonavir

Bartels, Hanni ; Decosterd, Laurent ; Battegay, Manuel ; Marzolini, Catia

In: Journal of Antimicrobial Chemotherapy, 2017, vol. 72, no. 9, p. 2574-2577

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    Titre
    • Darunavir concentrations in CSF of HIV-infected individuals when boosted with cobicistat versus ritonavir
    Auteur
    • Bartels, Hanni. Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland
    • Decosterd, Laurent. Laboratory of Clinical Pharmacology, Service of Biomedicine, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland
    • Battegay, Manuel. Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland
    • Marzolini, Catia. Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2017, vol. 72, no. 9, p. 2574-2577. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:332580
    Summary
    Abstract Objectives Cobicistat and ritonavir have different inhibitory profiles for drug transporters that could impact the distribution of co-administered drugs. We compared darunavir concentrations in CSF when boosted by cobicistat versus ritonavir relative to plasma concentrations and with WT HIV-1 IC50 and IC90. Methods An open, single-arm, sequential clinical trial (NCT02503462) where paired CSF and blood samples were taken from seven HIV-infected patients presenting with HIV-associated neurocognitive disorders (HAND) and treated with a darunavir/ritonavir (800/100 mg) once-daily regimen. Ritonavir was subsequently replaced by cobicistat and paired CSF and blood samples were obtained from the same patients after treatment with the darunavir/cobicistat (800/150 mg) once-daily regimen. Darunavir concentrations at the end of the dosing interval were quantified by LC-MS/MS. Results The median (IQR) darunavir concentrations in CSF with ritonavir and cobicistat boosting were 16.4 ng/mL (8.6-20.3) and 15.9 ng/mL (6.7-31.6), respectively (P = 0.58). The median (IQR) darunavir CSF:plasma ratios with ritonavir and cobicistat boosting were 0.007 (0.006-0.012) and 0.011 (0.007-0.015), respectively (P = 0.16). Darunavir concentrations in CSF exceeded the darunavir IC50 and IC90 by a median of 9.2- and 6.7-fold with ritonavir boosting, and by 8.9- and 6.5-fold with cobicistat boosting, respectively. All patients had darunavir CSF concentrations above the target inhibitory concentrations and remained virologically suppressed in the CSF and plasma. Conclusions This small study shows that cobicistat and ritonavir give comparable effective darunavir concentrations in CSF, thus suggesting that these boosters can be used interchangeably in once-daily darunavir regimens.