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

Ribera, Estebana; Azuaje, Carlosa; Lopez, Rosa Mb; Diaz, Marjoriea; Feijoo, Mariaa; Pou, Leonorc; Crespo, Manuela; Curran, Adriaa; Ocaña, Immaa; Pahissa, Alberta

doi: 10.1097/01.aids.0000226953.56976.ad
Clinical Science

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) μg/h/ml, respectively. Cmax values were 12.2 (10.7–14.5), 9.5 (6.8–13.9) and 10.0 (6.9–13.6) μg/ml, respectively. Cmin values were 9.1 (7.1–10.4), 5.6 (4.7–8.2) and 5.5 (4.2–7.5) μg/ml, respectively. No difference was observed for ATV AUC0–24 or Cmax between arms A and D. ATV Cmin 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.

From the aDepartment of Infectious Diseases, Hospital Universitari Vall d'Hebron, Barcelona, Spain

bDepartment of Pharmacy, Hospital Universitari Vall d'Hebron, Barcelona, Spain

cDepartment of Clinical Biochemistry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Received 22 November, 2005

Revised 12 January, 2006

Accepted 26 February, 2006

Correspondence to: E. Ribera, Servicio de Enfermedades Infecciosas, Hospital Universitari Vall Hebron, Paseo Vall Hebron 119-129, 08035 Barcelona, Spain. Tel: +34 934894497; fax: +34 934282762; e-mail: eribera@vhebron.net

© 2006 Lippincott Williams & Wilkins, Inc.