Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged >/=7 years

Item does not contain fulltextBACKGROUND: The Asian population, in general, has higher antiretroviral concentrations than those who are not Asian, but there are limited pharmacokinetic data for darunavir/ritonavir in Asian children. METHODS: Thai children aged >/=7 years and with body weight (BW)>/=20 kg who were on darunavir/ritonavir for >/=2 weeks underwent 12-h pharmacokinetics with blood sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing. Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to /=40 kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution. RESULTS: Of the 19 children, 8 were female, median age was 13 years (range 7-16) and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment was 11 months. The geometric mean values for darunavir were 60.3 hxmg/l for the area under the concentration-time curve at 0-12 h (AUC(0-12)), 8.3 mg/l for the maximum concentration (C(max)) and 3.1 for the concentration prior to the next dose (C(12)) with no differences between dosing groups. All had C(12) above the protein binding adjusted 50% effective concentration (EC(50)) of protease inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters were similar to those in non-Asian individuals from the DELPHI study, in which 13 of 20 with BW/=7 years who were on standard darunavir dosing with 100 mg ritonavir boosting had adequate and comparable darunavir AUC(0-12), C(max) and C(12) to non-Asian children who mainly used lower doses of ritonavir boosting. A ritonavir boosting dose of 100 mg can be used for children weighing >/=20 kg, particularly when lower dose formulations are unavailable or if intolerant to the solution

Early and late virologic failure after virologic suppression in HIV-infected Asian children and adolescents

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving. Setting: An Asian cohort in 16 pediatric HIV services across 6 countries. Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA >= 1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA >= 1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure. Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure. Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: Double blind randomised controlled trial

10.1136/bmj.f3039BMJ (Online)3467911-BMJO