Atazanavir and lopinavir/ritonavir: pharmacokinetics, safety and efficacy of a promising double-boosted protease inhibitor regimen

Objective: To assess the pharmacokinetics and tolerability of lopinavir (LPV), ritonavir (RTV) and atazanavir (ATV) as a double-boosted protease inhibitor regimen in HIV-infected adults.

Methods: Sixteen patients who started LPV/RTV (400/100 mg b.i.d.) and ATV (300 mg q.d.) were enrolled in the study group (arm A). LPV pharmacokinetics were compared to those of two historical groups: arm B, 15 patients who received LPV/RTV (400/100 mg b.i.d.); and arm C, 25 patients who received LPV/RTV/saquinavir (SQV) (400/100/ 1000 mg b.i.d.). ATV pharmacokinetics were compared to those of 15 consecutive patients who received ATV and RTV (300/100 mg q.d.) (arm D). Drug concentrations were measured by HPLC.

Results: LPV concentrations were significantly higher in arm A than in arms B and C. Median (interquartile range) LPV area under the curve (AUC)(0-12) values were 115.7 (99.8-136.5), 85.2 (68.3-109.2) and 85.1 (60.6-110.1) mu g/h/ml, respectively. C-min values were 12.2 (10.7-14.5), 9.5 (6.8-13.9) and 10.0 (6.9-13.6) mu g/ml, respectively. C,in values were 9.1 (7.1-10.4), 5.6 (4.7-8.2) and 5.5 (4.2-7.5) mu g/ml, respectively. No difference was observed for ATV AUC(0-24) or C-max between arms A and D. ATV C,in values were 1.07 (0,61-1.79) in arm A and 0.58 (0.32-0.83) in arm D (P = 0.001). Treatment was not discontinued in any patient because of adverse effects. At 24 weeks, viral load was < 50 copies/ml in 13 of 16 patients.

Conclusions: The combination of ATV and LPV/RTV provided high plasma concentrations of both PI, which seemed to be appropriate for patients with multiple prior therapeutic failures, yielding good tolerability and substantial antiviral efficacy.