Patricia Flynn1, Svitlana Komar, Stephane Blanche, Carlo Giaquinto, Antoni Noguera-Julian, Steven Welch, Erkki Lathouwers, Tom Van de Casteele, Thomas N Kakuda, Magda Opsomer. 1. From the *Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN; †Clinic for Treatment of HIV-infected Children, Kiev Children's Hospital, Kiev, Ukraine; ‡Department of Pediatric Immuno-Hematology, Hôpital Necker-Enfants Malades, Paris, France; §Department of Paediatrics, University of Padova, Padova, Italy; ¶Department of Pediatrics, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; ‖Department of Pediatrics, Birmingham Heartlands Hospital, Birmingham, United Kingdom; **Janssen Research & Development LLC, Titusville, NJ; and ††Janssen Research & Development, Beerse, Belgium.
Abstract
BACKGROUND: Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents. METHODS: Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve, HIV-1-infected adolescents (≥12 to <18 years, ≥40 kg) with zidovudine/lamivudine or abacavir/lamivudine. RESULTS: Twelve patients (67% female; median 14.4 years) were enrolled. After 24 and 48 weeks, respectively, 11 of 12 (92%) and 10 of 12 (83%) patients achieved viral load <50 copies/mL (intent-to-treat time-to-loss of virologic response); all had ≥1 log10 drop in viral load versus baseline. Median CD4 cell count increased by 175 and 221 cells/mm (intent-to-treat-noncompleter = failure) after 24 and 48 weeks, respectively. Eighty-three percent of patients were adherent to darunavir/ritonavir. One patient was never suppressed and 1 patient rebounded. No patients developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor. Eleven patients (92%) reported ≥1 adverse event (AE), considered in 2 patients to be at least possibly related to darunavir (gastrointestinal-related events and dizziness). Four patients had ≥1 serious AE. Three patients reported ≥1 grade 3/4 AE; no serious or grade 3/4 AEs were considered darunavir related. No patients discontinued because of AEs. CONCLUSIONS: Over 48 weeks, once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1-infected, antiretroviral-naïve adolescents (≥12 to <18 years). These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population.
BACKGROUND: Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents. METHODS: Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve, HIV-1-infected adolescents (≥12 to <18 years, ≥40 kg) with zidovudine/lamivudine or abacavir/lamivudine. RESULTS: Twelve patients (67% female; median 14.4 years) were enrolled. After 24 and 48 weeks, respectively, 11 of 12 (92%) and 10 of 12 (83%) patients achieved viral load <50 copies/mL (intent-to-treat time-to-loss of virologic response); all had ≥1 log10 drop in viral load versus baseline. Median CD4 cell count increased by 175 and 221 cells/mm (intent-to-treat-noncompleter = failure) after 24 and 48 weeks, respectively. Eighty-three percent of patients were adherent to darunavir/ritonavir. One patient was never suppressed and 1 patient rebounded. No patients developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor. Eleven patients (92%) reported ≥1 adverse event (AE), considered in 2 patients to be at least possibly related to darunavir (gastrointestinal-related events and dizziness). Four patients had ≥1 serious AE. Three patients reported ≥1 grade 3/4 AE; no serious or grade 3/4 AEs were considered darunavir related. No patients discontinued because of AEs. CONCLUSIONS: Over 48 weeks, once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1-infected, antiretroviral-naïve adolescents (≥12 to <18 years). These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population.
Authors: Kajal B Larson; Tim R Cressey; Ram Yogev; Andrew Wiznia; Rohan Hazra; Patrick Jean-Philippe; Bobbie Graham; Amy Gonzalez; Paula Britto; Vincent J Carey; Edward P Acosta Journal: J Pediatric Infect Dis Soc Date: 2015-01-28 Impact factor: 3.164
Authors: A Brochot; T N Kakuda; T Van De Casteele; M Opsomer; F L Tomaka; A Vermeulen; P Vis Journal: CPT Pharmacometrics Syst Pharmacol Date: 2015-06-19
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Authors: Erkki Lathouwers; Eric Y Wong; Kimberley Brown; Bryan Baugh; Anne Ghys; John Jezorwski; El Ghazi Mohsine; Erika Van Landuyt; Magda Opsomer; Sandra De Meyer Journal: AIDS Res Hum Retroviruses Date: 2019-10-21 Impact factor: 2.205