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



Jackson, Akil ORCID: 0000-0002-4574-544X, Else, Laura, Higgs, Christopher, Karolia, Zeenat, Khoo, Saye ORCID: 0000-0002-2769-0967, Back, David, Devitt, Emma, Pozniak, Anton and Boffito, Marta
(2018) Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naive HIV-1-infected individuals. HIV CLINICAL TRIALS, 19 (1). pp. 31-37.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Dual antiretroviral therapy, Pharmacokinetics, HIV antiviral pharmacology, Rilpivirine, Darunavir
Depositing User: Symplectic Admin
Date Deposited: 07 Jun 2018 11:44
Last Modified: 19 Jan 2023 06:38
DOI: 10.1080/15284336.2017.1408928
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3018515