PRINCE-1: safety and efficacy of atazanavir powder and ritonavir liquid in HIV-1-infected antiretroviral-naïve and -experienced infants and children aged > 3 months to < 6 years

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)-naı¨ve and -experienced children with HIV-1 infection aged ]3 months to B6 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 B10 kg 150 mg, 10 to B15 kg 200 mg and 15 to B25 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-naı¨ve. 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 B50 copies/mL and B400 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 B50 copies/mL, and 66.7, 73.7 and 85.7% had HIV-RNA B400 copies/mL, respectively) but did not differ meaningfully between ARV-naı¨ve and -experienced patients. Overall, the median change from baseline in CD4 cell count was 363 cells/mm3, 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-naı¨ve or -experienced paediatric population aged ]3 months to B6 years. No unexpected safety findings compared with those from previous ATV paediatric and adult studies were identified.