Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children.
OBJECTIVE
To assess the pharmacokinetics and 24-week efficacy and safety of dual boosted saquinavir/lopinavir/ritonavir combination in children.


METHODS
Twenty reverse transcription inhibitor-pretreated children at 2 centers in Thailand were treated with saquinavir/lopinavir/ritonavir in an open label, single arm, 6-month prospective study. The dosage was 50 mg/kg twice daily (bid) for saquinavir and 230/57.5 mg/m bid for lopinavir/ritonavir. Ten children also received lamivudine.


METHODS
Samples were collected for a 12-hour pharmacokinetic profile in all children. Plasma concentrations of saquinavir, lopinavir and ritonavir were determined using a validated high performance liquid chromatography technique.


RESULTS
At baseline, the median age was 8.5 years, with human immunodeficiency virus (HIV) RNA 4.9 log10 copies/mL, CD4 count 129 cells/microL and CD4%, 6.5%. Median area under the concentration curve at 0-12 hours and Cmin were 39.4 mg/L.h and 1.4 mg/L for saquinavir and 118 mg/L.hr and 5.9 mg/L for lopinavir. After 24 weeks of treatment, HIV RNA was suppressed below 400 copies/mL for 16 of 20 (80%) children (intent-to-treat analysis) and below 50 copies/mL for 12 of 20 children (60%), and CD4% (count) rose by a median of 6% (216 cells/microL). Median changes of triglyceride and total cholesterol were 56 and 36.5 mg/dL, respectively (P = 0.01). Lopinavir Cmin <1 and saquinavir Cmin <0.28 mg/L correlated with HIV RNA >400 copies/mL, and lopinavir Cmax >15 mg/L correlated with rises in cholesterol (P < 0.05).


CONCLUSIONS
Plasma drug concentrations of saquinavir, lopinavir and ritonavir were at the higher limits of expected ranges for adult treatment at approved dosages (1000/100 mg bid for saquinavir, 400/100 mg bid for lopinavir/ritonavir). The regimen was well-tolerated and had good efficacy at 24 weeks. This dual boosted protease inhibitor combination should be assessed in larger trials of reverse transcription inhibitor-experienced children.
Ananworanich
Jintanat
J
HIV Netherlands Australia Thailand Research Collaboration. jintanat.a.@chula.ac.th
Kosalaraksa
Pope
P
Hill
Andrew
A
Siangphoe
Umaporn
U
Bergshoeff
Alina
A
Pancharoen
Chitsanu
C
Engchanil
Chulapan
C
Ruxrungtham
Kiat
K
Burger
David
D
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir