Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients

摘要: To measure the in vivo variations of CYP3A activity induced by anti-HIV drugs human immunodeficiency virus (HIV)1-positive patients. A low oral dose midazolam (MID) (0.075 mg) was given to patients and 30-min total 1-OH (1-OHMID)/MID ratio determined. Patients were phenotyped either before introduction antiretroviral treatments (control group, 90 patients) or after a variable period treatment (56 patients). Twenty-one subjects underwent multiple phenotyping tests (before during course treatment). The median MID 3.51 control group (range 0.20–14.6). It 5-fold higher with efavirenz (28 patients; median, range: 16.0, 3.81–367; P<0.0001), 13-fold lower nelfinavir (18 0.27, 0.06–36.3; 17-fold efavirenz+ritonavir (three 0.21, 0.05–0.47; P=0.006), 50-fold ritonavir (four 0.07, 0.06–0.17; P=0.0007), 7-fold nevirapine+(ritonavir grapefruit juice) 0.48, 0.03–1.83; P=0.03). (P=0.01) (P=0.04) than although already strongly inhibited latter. low-dose test successfully used drugs. Efavirenz induces activity, while almost completely inhibits it. Nelfinavir decreases but lesser extent ritonavir. inhibition offsets inductive effects nevirapine administered concomitantly. Finally, no induction noticeable long-term administration at dosages (200 mg/day b.i.d.) standard (2,500 mg/day b.i.d.).