Dual Boosted Saquinavir/Lopinavir/Ritonavir at 24 Weeks Is Safe
and Potent in Nucleoside-pretreated Children
The
objective of the current study was to assess the pharmacokinetics
and 24-week efficacy and safety of dual
boosted saquinavir/lopinavir/ritonavir combination
in children.
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 (Epivir).
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 HIV RNA 4.9 log10
copies/mL, CD4
count 129 cells/microliter
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/microliter.
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).
Based
on these results, the authors conclude, “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.”
From
the HIV Netherlands Australia Thailand Research Collaboration;
Khon Kaen University, Khon Kaen, Thailand; Department of Pharmacology, University of
Liverpool, Liverpool, United Kingdom; UMC St. Radboud,
Nijmegen, the Netherlands; and Chulalongkorn
University, Bangkok, Thailand.
10/17/05
Reference
J
A Nanworanich
and others (theHIV-NAT 017 Study Team).
Pharmacokinetics and 24-Week Efficacy/Safety of Dual Boosted
Saquinavir/Lopinavir/Ritonavir in Nucleoside-Pretreated
Children. Pediatric Infectious Diseases Journal
24(10): 874-879. October 2005.
