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

Jackson, Akil, 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. ISSN 1528-4336, 1945-5771

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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 C<inf>max</inf>, C<inf>trough</inf>, 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:	22 May 2026 18:22
DOI:	10.1080/15284336.2017.1408928
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3018515
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