Pharmacokinetics and short-term efficacy of a double-boosted protease inhibitor regimen in treatment-naive HIV-1-infected adults.
OBJECTIVE
To study the pharmacokinetics and short-term efficacy of low and standard dose lopinavir/ritonavir and saquinavir combinations in Thai, human immunodeficiency virus (HIV)-infected, treatment-naive patients.


METHODS
In this open-label, 24-week, prospective study, 48 treatment-naive patients were randomized to lopinavir/ritonavir 400/100 mg+saquinavir 1000 mg twice daily (arm A), lopinavir/ritonavir 400/100 mg+saquinavir 600 mg twice daily (arm B), lopinavir/ritonavir 266/66 mg+saquinavir 1000 mg twice daily (arm C), or lopinavir/ritonavir 266/66 mg+saquinavir 600 mg twice daily (arm D). A 12 h. pharmacokinetic profile in all patients was performed. Plasma concentrations of saquinavir and lopinavir were determined using an HPLC technique. HIV-1 RNA was measured over 24 weeks.


RESULTS
Forty-three subjects were included in the pharmacokinetic analysis. The total exposure differed significantly for the different arms. Median values for lopinavir area under the curve at 0-12 h were 128.2, 119.2, 66.1 and 68.5 mg.h/L for arms A-D, respectively. For saquinavir, the median values were 36.9, 19.2, 25.3 and 12.4 mg.h/L for arms A-D, respectively. The proportion of patients having a viral load below 50 copies/mL at week 24 was 39% for arm A, 63% for arm B, 55.0% for arm C, and 69% for arm D.


CONCLUSIONS
The pharmacokinetic parameters for the different treatment arms were adequate. However, the proportion of subjects with an undectable viral load at week 24 was lower than anticipated.
van der Lugt
Jasper
J
HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center Bangkok, 104 Ratchadamri Road, Pathumwan, Bangkok 10330, Thailand. jasper.v@hivnat.org
Autar
Reshma Saskia
RS
Ubolyam
Sasiwimol
S
Garcia
Evian Fernandez
EF
Sankote
Jongkol
J
Avihingsanon
Anchalee
A
Avihingson
Anchalee
A
Chuenyam
Theshinee
T
Cooper
David A
DA
Lange
Joep
J
Phanuphak
Praphan
P
Wit
Ferdinand
F
Ruxrungtham
Kiat
K
Burger
David
D
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D011480:Protease Inhibitors