Background: We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads.
Settings: Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals.
Methods: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.
Results: Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine Cmax, Ctrough, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded.
Conclusions: rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.
Keywords: Darunavir; Dual antiretroviral therapy; HIV antiviral pharmacology; Pharmacokinetics; Rilpivirine.