Pharmacokinetics of darunavir/cobicistat and etravirine alone and co-administered in HIV-infected patients

Abstract

Objectives

To determine the effect of etravirine on the pharmacokinetics of darunavir/cobicistat and vice versa. Safety and tolerability of this combination were also evaluated.

Methods

Open-label, fixed-sequence trial in two cohorts of HIV-infected patients on therapy with darunavir/cobicistat 800/150 mg once daily (DRV cohort; n = 15) or etravirine 400 mg once daily (ETR cohort; n = 15). Etravirine or darunavir/cobicistat were added on days 1–14 and 1–7 in participants in the DRV or ETR cohort, respectively. Full pharmacokinetic profiles were obtained on days 0 and 14 in the DRV cohort, and on days 0 and 7 in the ETR cohort. Darunavir, cobicistat and etravirine pharmacokinetic parameters [AUC_0–24, C_max and trough concentrations in plasma (C₂₄)] were calculated for each individual by non-compartmental analysis and were compared using linear mixed-effects models. Adverse events and HIV-1 RNA in plasma were monitored.

Results

Etravirine co-administration decreased cobicistat AUC_0–24, C_max and C₂₄ by 30%, 14% and 66%, respectively. Although darunavir AUC_0–24 and C_max were unchanged by etravirine, darunavir C₂₄ was 56% lower for darunavir/cobicistat co-administered with etravirine relative to darunavir/cobicistat alone. Etravirine pharmacokinetics were unchanged by darunavir/cobicistat. Treatments were well tolerated, and HIV-1 RNA remained undetectable in all participants.

Conclusions

Although etravirine pharmacokinetics was unchanged by darunavir/cobicistat, there was a significant decrease in cobicistat exposure and in darunavir C₂₄ when darunavir/cobicistat was co-administered with etravirine. Boosting darunavir with ritonavir instead of with cobicistat may be preferred if darunavir is to be combined with etravirine in clinical practice.

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via IFTTT