Abstract
INTRODUCTION: PRINCE-1 is an ongoing prospective, international, multicentre, nonrandomized, two-stage clinical trial assessing safety and efficacy of once-daily atazanavir (ATV) powder boosted with ritonavir (RTV) liquid plus optimized dual nucleoside reverse-transcriptase inhibitor (NRTI) background therapy in antiretroviral (ARV)-naïve and -experienced children with HIV-1 infection aged ≥3 months to <6 years. METHODS: Children with HIV-1 infection without prior ATV exposure and with a screening HIV-1 RNA ≥1000 copies/mL were enrolled. The dosing of ATV powder, boosted with 80 mg RTV liquid, was based on three baseline weight bands (5 to <10 kg=150 mg, 10 to <15 kg=200 mg and 15 to <25 kg=250 mg). RESULTS: Of the 56 treated patients, 46 completed 48 weeks of therapy, 67.9% were from Africa and 60.7% were ART-naïve. Median ages at baseline were 6, 35 and 55 months, and proportions with HIV-1 RNA >100,000 were 85.7, 52.6 and 25% in the three baseline weight bands, respectively. No unexpected safety events occurred and no deaths were reported. Over 48 weeks, upper respiratory tract infections, diarrhoea, vomiting and Grade 3 to 4 hyperbilirubinaemia occurred in 35.7, 35.7, 28.6, and 9.4% of patients, respectively; five patients (8.9%) discontinued due to adverse events (AEs); and 11 patients (19.6%) experienced serious adverse events. At Week 48, using a modified intent-to-treat analysis (two patients were excluded because they switched to ATV capsules before Week 48), 61.1 and 74.1% of patients overall had an HIV-1 RNA level <50 copies/mL and <400 copies/mL, respectively. Virologic suppression rates increased across the lowest to highest baseline weight bands (47.6, 68.4 and 71.4% had HIV-1 RNA <50 copies/mL, and 66.7, 73.7 and 85.7% had HIV-RNA <400 copies/mL, respectively) but did not differ meaningfully between ARV-naïve and -experienced patients. Overall, the median change from baseline in CD4 cell count was +363 cells/mm(3), and the median change from baseline in CD4 percent was +7.5%. CONCLUSIONS: ATV powder boosted with RTV liquid once daily plus optimized dual NRTI background therapy was effective and well tolerated in this ART-naïve or -experienced paediatric population aged ≥3 months to <6 years. No unexpected safety findings compared with those from previous ATV paediatric and adult studies were identified.