Hybrid stochastic framework predicts efficacy of prophylaxis against HIV: An example with different dolutegravir prophylaxis schemes
Fig 3
Population pharmacokinetics of dolutegravir (DTG).
A: Pharmacokinetic model. Concentrations within the central compartment with bioavailability-adjusted volume Vc/F correspond to measured plasma concentrations of DTG (indicated by the blue pin). Parameters ka, Q/Fbio and CL/Fbio denote the uptake and bioavailability-adjusted inter-compartimental and drug clearance rate respectively and Vp/Fbio denotes the bioavailability adjusted volume of the peripheral compartment (which summarizes all ‘deep’ compartments, which are not in rapid exchange with the plasma). B: Predicted plasma concentration time profiles of dolutegravir (DTG) for the first four days after initiation of a once daily 50mg oral regimen (N = 300 virtual patients). The red line depicts the median predicted concentrations, whereas the dark- and light grey areas present the quartile range and 5–95% range respectively. Predicted (red line, grey areas) and measured plasma concentrations during 24h after drug intake in steady state (panel C) and after cessation of drug intake (panel D). Black circles and thin dashed lines represent DTG plasma concentration profiles in healthy volunteers (n = 17 concentration time profiles, 270 data points in total), whereas yellow circles, purple squares, grey diamonds and cyan triangles are DTG plasma concentration measurements in HIV patients (n = 39) observed 1, 2, 3 and 4 weeks after switching from efavirenz-based therapy to dolutegravir. Altogether, 354 plasma concentration measurements from 56 individuals are depicted.