Background: The three-direct acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir and dasabuvir ± ribavirin (RBV) is approved for treatment of HCV GT1/HIV-1 co-infection. Results of a pharmacokinetic substudy of 3D and darunavir are presented.
Methods: HCV/HIV-1 infected subjects were randomized to maintain a darunavir 800 mg once daily (QD) or switch to a darunavir 600 mg twice daily (BID) based antiretroviral regimen. On Study Day 1, subjects received 3D and RBV plus darunavir for 12 weeks. Pharmacokinetic parameters were compared for darunavir with and without 3D. Pharmacokinetic parameters of 3D were compared to historical data.
Results: Ten subjects received darunavir QD and 12 subjects received darunavir BID. The central value ratios (90% confidence interval [CI]) for darunavir Cmax, AUC24 and C24 administered QD with 3D vs. alone were 0.92 (0.72, 1.18), 0.83 (0.71, 0.98) and 0.64 (0.44, 0.93), respectively. The ratios (90% CI) for darunavir Cmax, AUC12 and C12 administered BID with 3D were 0.92 (0.76, 1.12), 0.88 (0.73, 1.05) and 0.73 (0.58, 0.92), respectively. Exposures of 3D were similar or slightly lower compared with historical data. All darunavir trough concentrations (Ctrough) associated with an HIV-1 RNA >40 copies/mL were above the darunavir EC50 of 550 ng/mL for resistant virus.
Conclusions: The 3D regimen with darunavir QD or BID did not affect darunavir Cmax and AUC, whereas darunavir Ctrough decreased. Changes in pharmacokinetic parameters of 3D were not considered clinically significant. Episodes of intermittent HIV-1 viremia were infrequent and not associated with darunavir Ctrough values below 550 ng/mL. (This study has been registered at ClinicalTrials.gov under identifier NCT01939197.)
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