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

Details

Serval ID
serval:BIB_C9AD206973FE
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Darunavir concentrations in CSF of HIV-infected individuals when boosted with cobicistat versus ritonavir.
Journal
The Journal of antimicrobial chemotherapy
Author(s)
Bartels H., Decosterd L., Battegay M., Marzolini C.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
01/09/2017
Peer-reviewed
Oui
Volume
72
Number
9
Pages
2574-2577
Language
english
Notes
Publication types: Clinical Trial ; Journal Article
Publication Status: ppublish
Abstract
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.
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.
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.
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.

Keywords
Adult, Aged, Anti-HIV Agents/blood, Anti-HIV Agents/cerebrospinal fluid, Anti-HIV Agents/therapeutic use, Cobicistat/administration & dosage, Cobicistat/blood, Cobicistat/therapeutic use, Darunavir/blood, Darunavir/cerebrospinal fluid, Darunavir/therapeutic use, Drug Therapy, Combination, Female, HIV Infections/drug therapy, HIV Protease Inhibitors/blood, HIV Protease Inhibitors/cerebrospinal fluid, HIV Protease Inhibitors/therapeutic use, HIV-1/drug effects, Humans, Male, Middle Aged, Ritonavir/administration & dosage, Ritonavir/therapeutic use, Tandem Mass Spectrometry
Pubmed
Web of science
Create date
19/06/2017 9:09
Last modification date
20/08/2019 16:44
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