Background: Novel antiretroviral formulations that are palatable, safe, and effective are needed for infants and children.
Methods: PRINCE-2 is an ongoing clinical trial assessing safety, efficacy, and palatability of once-daily atazanavir powder formulation boosted with ritonavir (ATV + RTV) plus optimized dual nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children 3 months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg = 150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg = 250/80 mg; and 25 to <35 kg = 300/100 mg.
Results: Of 99 treated children, 83.8% and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48 weeks, the most common adverse events were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious adverse events occurred in 20.2% of patients. Laboratory grade 3-4 hyperbilirubinemia occurred in 9.2% and elevated total/pancreatic amylase in 33.7%/3.1%. At week 24, proportions with virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis) across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35 (54.3%) and 5/8 (62.5%), respectively. Virologic suppression was similar in antiretroviral-naïve/experienced patients and lowest in the 5 to <10 kg = 200/80 mg group, likely because of higher baseline HIV-1 RNA and discontinuation (66.7%). Overall, virologic suppression at weeks 24 (46.5%) and 48 (43.0%) was comparable. At week 48, 83.3% and 74.1% of caregivers reported no trouble giving ATV powder and RTV, respectively.
Conclusions: ATV powder palatability, efficacy and lack of unexpected safety findings support its use for HIV-1-infected children ≥3 months to <11 years.