Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals
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|ClinicalTrials.gov Identifier: NCT02503462|
Recruitment Status : Terminated (No additional patients fulfilling the inclusion criteria)
First Posted : July 21, 2015
Last Update Posted : February 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|AIDS-related Dementia Complex||Drug: Darunavir Drug: ritonavir Drug: cobicistat||Phase 4|
Cobicistat is a new pharmacokinetic enhancer or booster of the HIV protease inhibitor darunavir. Cobicistat is distinct from the conventional booster ritonavir in that cobicistat presents a more selective inhibition of the enzymes metabolizing drugs. In addition, cobicistat is a weaker inhibitor of the efflux drug transporters expressed at the level of the blood-brain barrier (i.e. P-glycoprotein (P-gp) and breast cancer resistance Protein (BCRP)). A weaker inhibition of these efflux transporters could possibly result in less darunavir entering the brain when boosted by cobicistat as compared to a boosting by ritonavir. Such a difference could potentially be critical in patients with HIV-associated neurocognitive disorders as sufficient drug levels are needed to efficiently inhibit HIV replication inside the brain.
The aim of this study is to determine whether the boosting of darunavir by cobicistat results effectively in lower darunavir concentrations in the CSF as compared to a boosting by ritonavir. The study will be performed in HIV infected patients presenting HIV associated neurocognitive disorders (HAND) and requiring a lumbar puncture for clinical reasons. In addition, the patients will be only eligible if the are treated or if they qualify for a darunavir/ritonavir (800/100 mg once daily) containing regimen. Darunavir concentrations will be measured simultaneously in the CSF and plasma (CSF/plasma ratio) first with the ritonavir boosting and subsequently with the cobicistat boosting.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals|
|Study Start Date :||July 2015|
|Actual Primary Completion Date :||January 2017|
|Actual Study Completion Date :||January 2017|
Experimental: darunavir/ritonavir vs cobicistat
All HIV infected patients will be treated with a darunavir/ritonavir (800/100 mg) once daily containing regimen. Darunavir/ritonavir concentrations will be measured simultaneously in CSF and plasma after 1 month of treatment. The treatment will be switched to darunavir/cobicistat (800/150 mg) once daily and darunavir/cobicistat levels will be measured in CSF and plasma after 1 month of treatment.
darunavir 800 mg once daily will be first given together with ritonavir 100 mg once daily for one month (period 1) and then darunavir 800 mg once daily will be given together with cobicistat 150 mg once daily for one month (period 2). Afterwards, all patients will be switched back to darunavir/ritonavir (800/100 mg once daily).
Other Name: Prezista
ritonavir 100 mg once daily will be used to boost darunavir 800 mg once daily (period 1).
Other Name: Norvir
cobicistat 150 mg once daily will be used to boost darunavir 800 mg once daily (period 2).
Other Name: Tybost
- Cerebrospinal fluid/plasma concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat [ Time Frame: 1 month ]darunavir concentrations (ng/ml) in the cerebrospinal fluid when coadministered with ritonavir versus cobicistat relative to the corresponding concentrations of darunavir in the plasma
- Cerebrospinal fluid concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat relative to the concentration of darunavir (ng/ml) inhibiting 50% (IC50) or 90% (IC90) of the viral replication [ Time Frame: 1 month ]darunavir concentrations (ng/ml) in the cerebrospinal fluid when coadministered with ritonavir versus cobicistat relative to darunavir concentrations (ng/ml) suppressing HIV replication by 50% and 90% (IC50 and IC90)
- Proportion of responders (HIV RNA < 50 copies/ml in CSF) for darunavir/ritonavir versus darunavir/cobicistat [ Time Frame: 1 month ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02503462
|Division of Infectious Diseases, University Hospital Basel|
|Basel, BS, Switzerland, 4031|
|Principal Investigator:||Manuel Battegay||University Hospital, Basel, Switzerland|