Treatment simplification to once daily darunavir/ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients

Background: We explored a treatment simplification strategy to darunavir/ritonavir 900/100 mg once dally guided by the darunavir virtual Inhibitory quotient (vlQ) in patients receiving salvage therapy with darunavir/ritonavir 600/100 mg twice daily. Methods: Open-label, randomized pilot study in HIV-infected patients on darunavir/ritonavir 600/100 mg twice dally (viral load <50 copies/ml; darunavir vlQ >2). Thirty patients were randomized to darunavir/ritonavir 900/100 mg once daily (once-daily group, n=15) or 600/100 mg twice dally (twice-daily group, n=15). Viral load, blood chemistry, and darunavir and ritonavir trough plasma concentrations (C trough) were determined up to 48 weeks. If the darunavir vlQ fell to <1.5, the dosage was switched to 600/100 mg twice daily. The primary end point was the percentage of 48-week treatment failure. Results: Patients had taken a mean 11.6 (SD ±3.9) antiretroviral regimens before darunavir/ritonavir administration. The proportion of patients without 48-week treatment failure was 86.7% In both groups. The median (interquartile range [IQR]) darunavir Ctrough decreased from 3.09 mg/l (IQR 2.43-3.93) at baseline to 1.60 mg/l (IQR 1.25-2.04) at week 48 (P=0.001) in the once-daily group. Three once-daily group patients switched to darunavir/ritonavir 600/100 mg twice dally. Fewer patients had triglyceride levels >200 mg/dl at week 48 in the once-daily group (20.0%) than in the twice-daily group (20.0% versus 57.1%; P=0.046). Conclusions: Treatment simplification to darunavir/ritonavir 900/100 mg once dally guided by the darunavir vlQ in treatment-experienced HIV-infected patients receiving darunavir/ritonavir 600/100 mg twice-daily seems to be safe enough to be tested in adequately powered clinical trials.