Pharmacokinetics of darunavir/cobicistat and etravirine alone and co-administered in HIV-infected patients | Fundació Lluita contra la Sida

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

11/12/2017

Autors: José Moltó, Adrian Curran, Cristina Miranda, Elizabeth Challenger, José Ramón Santos, Esteban Ribera, Saye Khoo, Marta Valle and Bonaventura Clotet

Revista: Journal of Antimicrobial Chemotherapy (JAC)

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 800/150mg once daily (DRV cohort; n"15) or etravirine 400mg 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 profileswere 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 [AUC0–24, Cmax and trough concentrations in plasma (C24)] were calculated for each individual by non-compartmental analysis and were compared using linearmixed-effectsmodels. Adverse events and HIV-1 RNA in plasmaweremonitored.


Results: Etravirine co-administration decreased cobicistat AUC0–24, Cmax and C24 by 30%, 14% and 66%, respectively. Although darunavir AUC0–24 and Cmax 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.