06 July 2013
More than three quarters of children with antiretroviral experience reached an undetectable viral load with a regimen containing darunavir/ritonavir (DRV/RTV) after 48 weeks in the ARIEL trial. The investigators recorded only 3 virologic failures and one dropout because of adverse events in this 21-child study.
The US Food and Drug Administration licensed darunavir/ritonavir for antiretroviral-experienced children from 3 to 6 years old and weighing 10 to under 20 kg on the basis of week-24 ARIEL results. At the 7th IAS Conference in Kuala Lumpur, researchers detailed 48-week findings from this phase 2, open-label, 5-country trial. All study participants had taken antiretroviral therapy for at least 12 weeks, had a viral load above 1000 copies/mL, and had fewer than 3 darunavir-associated resistance mutations.
After 2 weeks of treatment and pharmacokinetic analysis, the researchers selected darunavir/ritonavir doses of 25/3 mg/kg twice daily for children weighing 10 to under 15 kg and 375/50 mg/kg twice daily for those weighing 15 to under 20 kg. All children took oral suspension darunavir/ritonavir along with two or three nucleosides selected by the investigator.
Eleven of 21 study participants were girls; 12 were black or African American, 6 were white, 2 were mixed race, and 1 was Asian. Children had a median age of 4.4 years (range 3 to 6). Viral load at study entry averaged about 22,000 copies/mL, and initial median CD4 count was 927. Children had few PI mutations or darunavir-specific mutations.
Through an average 48 weeks of treatment, only 1 child had an adverse event possibly related to darunavir (QT prolongation on ECG), and only 1 child stopped treatment (because of grade 2 vomiting probably related to ritonavir). No children had clinically relevant changes in lab values.
After 48 weeks of treatment, a time-to-loss-of-virologic-response analysis determined that 81% of children had a viral load below 50 copies and 85.7% had a viral load below 400 copies/mL. The FDA-favored snapshot analysis determined that 71.4% of children had a viral load below 50 copies at week 48. During the 48 weeks of treatment, CD4 percent rose an average 4%.
Of the 2 children who had darunavir-related resistance mutations when ARIEL began, both had a viral load below 50 copies at weeks 24 and 48. Of the 3 children with virologic failure at week 48, 2 never reached an undetectable viral load and 1 had a viral load rebound. Two of the 3 children with virologic failure had genotypes for resistance mutations at weeks 0 and 48; no protease inhibitor or nucleoside mutations emerged in either, and both children remained susceptible to darunavir and to nucleosides in the regimen.
Source: A. Violari, R. Bologna, N. Kumarasamy, et al. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients aged 3 to < 6 Years: week 48 analysis of the ARIEL trial. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract MOAB0102.
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