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.
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.
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.
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.
From the *Khon Kaen University, Khon Kaen; †The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; ‡Radboud University Nijmegen Medical Center, The Netherlands; §Chulalongkorn University, Bangkok, Thailand; ¶Roche, Nutley, NJ; and the ∥South East Asia Research Collaboration with Hawaii (SEARCH), Bangkok, Thailand.
Accepted for publication January 29, 2008.
Supported by funds from Roche and Abbott.
The funding source had no role in the analysis of this data. For the reporting of the results, the manuscript was reviewed by Roche and Abbott as a courtesy without affecting the integrity of the data. Malte Schutz, an employee of Roche, is one of the authors who contributed to the design and the report of this study.
Conflict of interest: Pope Kosalaraksa and Torsak Bunupuradah have received travel grants from Roche. Jintanat Ananworanich has received travel grants and honorarium from Roche.
Kiat Ruxrungtham has received travel grants, consultancy fees and honoraria from Roche, Abbott, Merck, Sharp and Dohme, and Bristol-Myers-Squibb. Malte Schutz is an employee of Roche. Other authors declare no conflict of interest.
Address for correspondence: Torsak Bunupuradah, MD, HIV-NAT, The Thai Red Cross AIDS Research Center, 104 Rajdumri Road, Pathumwan, Bangkok, Thailand 10330. E-mail: firstname.lastname@example.org.