Avy Violari1, Rosa Bologna, Nagalingeswaran Kumarasamy, Jose Henrique Pilotto, Annemie Hendrickx, Thomas N Kakuda, Erkki Lathouwers, Magda Opsomer, Tom Van de Casteele, Frank L Tomaka. 1. From the *Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; †Helios Salud, Buenos Aires, Argentina; ‡Gaitonade Center for AIDS Research and Education (YRG CARE), VHS, Chennai, India; §Department of Infectious Diseases, Hospital Geral De Nova Iguacu & Laboratório de AIDS e Imunologia Molecular, Fiocruz/IOC, Rio De Janeiro, Brazil; ¶Janssen Infectious Diseases BVBA, Beerse, Belgium; and ‖Janssen Research & Development LLC, Titusville, New Jersey.
Abstract
BACKGROUND: ARIEL (Darunavir in treatment-experienced pediatric population) was a phase II, open-label study assessing safety and antiviral activity of darunavir/ritonavir twice daily with an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected pediatric patients (3 to <6 years, weighing 10 to <20 kg). METHODS: The study consisted of an initial 4-week screening period, 48 weeks of treatment and a 4-week follow-up period. Patients initially received darunavir/ritonavir 20/3 mg/kg twice-daily for 2 weeks. Following review of pharmacokinetic, safety and antiviral data, the doses of darunavir/ritonavir were adjusted to 25/3 mg/kg twice-daily for patients <15 kg, and 375/50 mg twice-daily for patients 15 to <20 kg. RESULTS: Of the 34 patients screened, 21 were treated (median treatment duration 48.6 weeks). Darunavir plus an OBR was well tolerated over 48 weeks, with no new safety concerns, and a comparable safety profile to that seen in older children and adults. All treatment-emergent lipid-related and glucose-related laboratory abnormalities were grade 1 or 2. At week 48, 17 of 21 patients (81.0%) had a confirmed virologic response (intent-to-treat, time-to-loss of virologic response). Improvements in height and weight were seen during the study. CONCLUSIONS: No new safety concerns were observed over a 48 week period. These results led to lowering the age to 3 years at which darunavir/ritonavir is indicated for use in treatment-experienced pediatric patients. This study also established doses of darunavir to use in treatment-experienced, HIV-1-infected patients aged 3 to <6 years. A high virologic response was observed with this dose. No development of resistance was observed in patients who experienced virologic failure.
BACKGROUND: ARIEL (Darunavir in treatment-experienced pediatric population) was a phase II, open-label study assessing safety and antiviral activity of darunavir/ritonavir twice daily with an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected pediatricpatients (3 to <6 years, weighing 10 to <20 kg). METHODS: The study consisted of an initial 4-week screening period, 48 weeks of treatment and a 4-week follow-up period. Patients initially received darunavir/ritonavir 20/3 mg/kg twice-daily for 2 weeks. Following review of pharmacokinetic, safety and antiviral data, the doses of darunavir/ritonavir were adjusted to 25/3 mg/kg twice-daily for patients <15 kg, and 375/50 mg twice-daily for patients 15 to <20 kg. RESULTS: Of the 34 patients screened, 21 were treated (median treatment duration 48.6 weeks). Darunavir plus an OBR was well tolerated over 48 weeks, with no new safety concerns, and a comparable safety profile to that seen in older children and adults. All treatment-emergent lipid-related and glucose-related laboratory abnormalities were grade 1 or 2. At week 48, 17 of 21 patients (81.0%) had a confirmed virologic response (intent-to-treat, time-to-loss of virologic response). Improvements in height and weight were seen during the study. CONCLUSIONS: No new safety concerns were observed over a 48 week period. These results led to lowering the age to 3 years at which darunavir/ritonavir is indicated for use in treatment-experienced pediatric patients. This study also established doses of darunavir to use in treatment-experienced, HIV-1-infectedpatients aged 3 to <6 years. A high virologic response was observed with this dose. No development of resistance was observed in patients who experienced virologic failure.
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