Effect of body weight and composition on efavirenz, atazanavir or darunavir concentration.

Background.-To compare the steady state plasma concentrations (Css) of three antiretroviral drugs in both normal and overweight patients, and to determine the relationship between Css and fat mass (FM) or lean body mass. Methods.-Patients treated for more than 6 months once daily with one of the antiretroviral drugs: efavirenz (EFV) 600 mg, atazanavir boosted with ritonavir (ATV-r) 300 mg/100 mg, or darunavir boosted with ritonavir (DRV-r) 800 mg/100 mg, combined with two nucleoside analogues, were enrolled prospectively. One at steady state, plasma samples for the assessment of drug concentration were taken and body composition was assessed by bioelectrical impedance. Results.-One hundred and thirty-nine patients were enrolled (46, 45 and 48 in the groups EFV, ATV-r and DRV-r respectively). Their mean age was 46.2+/-10.4 years, 58% were male, 55.4% were from Sub Sahara African (SSA); body mass index (BMI) was 25.4+/-4.4 kg/m(2). Mean drug plasma Css of the three drugs did not differ according to BMI group. DRV-r Css tended to be higher in patients with BMI >= 25 kg/m(2) (2896.7+/-1689 versus 2091.9+/-1038, P=0.09) and was significantly correlated with FM (r=0.3, P=0.02). In subgroup analysis, the effect of FM on DRV-r Css was significant in patients from SSA (r=0.4, P=0.04). Conclusions Css result from many factors and body composition has been shown to only weakly influence interindividual variability but should be investigated in morbidly obese patients treated with DRV-r. (C) 2017 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.