Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks.
OBJECTIVE
To assess the 48-week efficacy, safety, pharmacokinetics, and resistance of double boosted protease inhibitors (PI), saquinavir (SQV), and lopinavir/ritonavir (LPV/r), in children who have failed nucleoside reverse transcription inhibitors /non-nucleoside reverse transcription inhibitors-based regimens.


METHODS
Fifty children at 2 sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4, HIV-RNA viral load (VL), plasma drug concentrations and safety laboratory evaluations were monitored. Virologic failure was defined as having 2 consecutive VL >400 copies/mL after week 12 of therapy. Intention to treat analysis was performed.


RESULTS
Baseline data were a median age of 9.3 years (interquartile range [IQR]: 7.1-11.2), Center for Disease Control and Prevention (CDC) classification N:A:B:C 4%:14%:68%:14%, VL 4.8 log10 (IQR: 4.5-5.1), CD4 7% (IQR: 3-9.5). At 48 weeks, 3 had died of bacterial infection but no cases had progressed CDC classification. Median CD4% rise was 9 (IQR: 5-16) and median HIV RNA reduction was -2.8 log10 (IQR: -3.2 to -1.4), both P < 0.001. Thirty-nine (78%) and 32 (64%) children had VL <400 and <50 with significant differences between the 2 sites. Five children (10%) had VL failure as a result of poor adherence to the drug regimen but no one had major PI mutations. Median serum cholesterol and triglyceride increased significantly (+35 mg/dL, +37 mg/dL, respectively, both P < 0.001). Mean minimum plasma concentrations (Cmin) of LPV and SQV were 4.6 and 1.24 mg/L, respectively.


CONCLUSIONS
Double boosted SQV/LPV/r resulted in significant CD4 rise and VL decline at 48 weeks. Hyperlipidemia was common. Cmin of both PIs exceeded therapeutic concentrations. Poor adherence caused failure in 10%. No major PI mutations were found.
Kosalaraksa
Pope
P
Khon Kaen University, Khon Kaen, Thailand.
Bunupuradah
Torsak
T
Engchanil
Chulapan
C
Boonrak
Pitch
P
Intasan
Jintana
J
Lumbiganon
Pagakrong
P
Burger
David
D
Ruxrungtham
Kiat
K
Schutz
Malte
M
Ananworanich
Jintanat
J
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001774:Blood Chemical Analysis; D018791:CD4 Lymphocyte Count; D002648:Child; D002784:Cholesterol / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D061466:Lopinavir; D008297:Male; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019258:Saquinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013785:Thailand; D016312:Treatment Refusal; D014280:Triglycerides / Q000097:blood; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D014280:Triglycerides; D061466:Lopinavir; D002784:Cholesterol; D019258:Saquinavir; D019438:Ritonavir