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Background: Several strategies aiming at simplifying maintenance antiretroviral therapy without jeopardizing efficacy are being explored to improve long term tolerability, adherence and reduce costs.
This sub-study was conducted in the setting of the ANRS-165 Darulight trial to evaluate DRV and RTV plasma pharmacokinetic parameters in patients switching from DRV/RTV (800/100mgQD) containing regimen to DRV/RTV (400/100mg QD).
Methods: Patients enrolled in this multicenter, open-label, phase II single arm trial with plasma HIV-RNA (pVL)< 50c/mL for ≥12 months while receiving stable DRV/RTV (800/100mg QD)+2 NRTIs were offered to participate in this pharmacokinetic sub-study. Intensive 24h pharmacokinetic blood sampling was performed at D0 (before the switch) and 12 weeks after switching to DRV/RTV (400/100 mg QD) (W12). Total and unbound (DRV) and total (RTV) plasma concentrations were determined by UPLC-MS/MS. Steady-state pharmacokinetic parameters (AUC, Cmin, Cmax, t1/2) were determined by a non-compartmental analysis. Paired Geometric Mean Ratio (GMR; IC90%) (W12/D0) was calculated (Wilcoxon test). Apparent Clearance (Cl/F) and distribution volume (Vd/F) and effect of RTV AUC were assessed by a non-linear mixed effects modelling approach, using Monolix software.
Results: Fifteen men were included and 12 full pharmacokinetic pairs (W12/D0) were available. Median age was 42 years (IQR, 41-47). Pharmacokinetic parameters are presented in Table. DRV and RTV half-lives remained unchanged. DRV and RTV Cl/F and Vd/F were determined using one-compartment model with first order absorption and linear elimination. DRV Cl/F and Vd/F were 28.4L/h (RSE (relative standard error) 22%) and 199L (RSE16%). RTV Cl/F and Vd/F were 21.3L/h (RSE7%) and 171L (RSE9%). RTV AUC did not appear to be of significant effect on Cl/F.
Conclusions: In HIV-infected patients receiving maintenance therapy with DRV/RTV (800/100mg QD)+2 NRTIs, a reduction of DRV/RTV to 400/100mg QD was associated with non-significant decreases of total DRV AUC and total/unbound DRV Cmin and a small decrease of unbound DRV AUC. Unexpectedly, RTV exposure slightly increased with the reduced DRV dosing regimen.

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