Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks.
BACKGROUND
This study aimed to assess the long-term efficacy, safety and use of therapeutic drug monitoring (TDM) of a double-boosted protease inhibitor (PI) combination, saquinavir (SQV) and lopinavir/ritonavir (LPV/r), in Thai HIV type-1 (HIV-1)-infected children who had failed on reverse transcriptase inhibitors.


METHODS
In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4(+) T-cell count and percentage, viral load (VL; HIV-1 RNA), minimum plasma drug concentrations (C(min)) and drug safety laboratory evaluations were monitored. Virological failure was defined as having two consecutive VL measures >400 copies/ml after week 12. An intention-to-treat analysis was performed.


RESULTS
Baseline data were a median age of 9.3 years (interquartile range [IQR] 7.1-11.2), VL 4.8 log(10) copies/ml (IQR 4.5-5.1) and CD4(+) T-cell percentage 7% (IQR 3.0-9.5). CDC classifications were N=4%, A=14%, B=68% and C=14% of participants. Median CD4(+) T-cell percentage and CD4(+) T-cell count increase were 14% (IQR 7-19) and 558 cells/mm(3) (IQR 308-782), respectively (both P<0.001). Overall, 37 (74%) children achieved VL<50 copies/ml with significant differences between sites (90% versus 63%). Over 96 weeks, 10 patients had virological failure. Total cholesterol and high-density lipoprotein increased significantly over time, whereas the triglycerides and low-density lipoprotein did not. Approximately 50% of participants reported no change in body shape, and 33%, 43% and 39% reported fatter arms, face and abdomen, respectively. LPV and SQV C(min) were high and stable over time.


CONCLUSIONS
Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close follow-up. On the basis of the TDM results, PI dose reduction in this population should be considered.
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand.
Torsak
T
Bunupuradah
Jasper
J
van der Lugt
Pope
P
Kosalaraksa
Chulapan
C
Engchanil
Pitch
P
Boonrak
Thanyawee
T
Puthanakit
Tawan
T
Mengthaisong
Apicha
A
Mahanontharit
Pagakrong
P
Lumbiganon
Emily
E
Tompkins
David
D
Burger
Kiat
K
Ruxrungtham
Jintanat
J
Ananworanich
D000293:Adolescent; D002648:Child; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects*; D013785:Thailand; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir