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) microg/h/ml, respectively. C(max) values were 12.2 (10.7-14.5), 9.5 (6.8-13.9) and 10.0 (6.9-13.6) microg/ml, respectively. C(min) values were 9.1 (7.1-10.4), 5.6 (4.7-8.2) and 5.5 (4.2-7.5) microg/ml, respectively. No difference was observed for ATV AUC0-24 or C(max) between arms A and D. ATV C(min) 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.
Ribera
Esteban
E
Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Paseo Vall Hebron 119-129, 08035 Barcelona, Spain. eribera@vhebron.net
Azuaje
Carlos
C
Lopez
Rosa M
RM
Diaz
Marjorie
M
Feijoo
Maria
M
Pou
Leonor
L
Crespo
Manuel
M
Curran
Adria
A
Ocaña
Imma
I
Pahissa
Albert
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D010865:Pilot Projects; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir