Mark F Cotton1, Afaaf Liberty2, Indiana Torres-Escobar3, Maria Isabel Gonzalez-Tome4, Jurgen Lissens5, Luna Zaru6, Isabelle Klauck7, Daniela Cambilargiu8, Cheryl Pikora9, Todd A Correll10. 1. From the Children's Infectious Diseases Clinical Research Unit, Department of Pediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa. 2. Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa. 3. Faculty of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico. 4. Pediatric Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. 5. Bristol-Myers Squibb, Braine L'Alleud, Belgium. 6. Bristol-Myers Squibb, Hopewell, New Jersey. 7. Bristol-Myers Squibb, Rueil-Malmaison, France. 8. Bristol-Myers Squibb, Buenos Aires, Argentina. 9. Bristol-Myers Squibb, Wallingford, Connecticut. 10. Bristol-Myers Squibb, Princeton, New Jersey.
Abstract
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 receivedATV + 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.
RCT Entities:
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-infectedchildren ≥3 months to <11 years.
Authors: Laura Saint-Lary; Marc Harris Dassi Tchoupa Revegue; Julie Jesson; Françoise Renaud; Martina Penazzato; Claire L Townsend; John O'Rourke; Valériane Leroy Journal: Front Pediatr Date: 2022-05-23 Impact factor: 3.569
Authors: Hylke Waalewijn; Anna Turkova; Natella Rakhmanina; Tim R Cressey; Martina Penazzato; Angela Colbers; David M Burger Journal: Ther Drug Monit Date: 2019-08 Impact factor: 3.681