Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals

• Published in: HIV clinical trials Vol. 19; no. 1; p. 31
• Main Authors: Jackson, Akil, Else, Laura, Higgs, Christopher, Karolia, Zeenat, Khoo, Saye, Back, David, Devitt, Emma, Pozniak, Anton, Boffito, Marta
• Format: Journal Article
• Language: English
• Published: England 01.02.2018
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Area Under Curve; Darunavir - administration & dosage; Darunavir - blood; Darunavir - pharmacokinetics; Darunavir - therapeutic use; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - pharmacokinetics; HIV Protease Inhibitors - therapeutic use; HIV-1; Humans; Male; Middle Aged; Rilpivirine - administration & dosage; Rilpivirine - blood; Rilpivirine - pharmacokinetics; Rilpivirine - therapeutic use; Ritonavir - administration & dosage; Ritonavir - blood; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; Viral Load; Young Adult; HIV antiviral pharmacology; Darunavir; Pharmacokinetics; Rilpivirine; Dual antiretroviral therapy
• ISSN: 1945-5771
• DOI: 10.1080/15284336.2017.1408928

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. Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals. 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. 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 C , C , AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded. 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.