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Dolutegravir Effective and Safe in ART-Experienced 6- to 12-Year-Olds
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Dolutegravir, an integrase inhibitor licensed for children 12 to 18 years old in many countries, proved potent and safe in an open-label study of 23 children 6 to 12 years old, most of them living in the United States [1]. The FDA is considering this antiretroviral for 6- to 12-year-old children.
IMPAACT P1093 is an ongoing phase 1/2 study of dolutegravir in children and adolescents. This analysis focused on children from 6 to 12 years old without integrase inhibitor experience and taking a failing antiretroviral regimen for at least 12 weeks or off antiretrovirals for 4 weeks. Participants needed at least one fully active antiretroviral to take with dolutegravir. From day 1 to day 10, children took dolutegravir alone or dolutegravir plus failing antiretrovirals. After an intensive pharmacokinetic analysis between days 5 and 10, researchers continued dolutegravir and optimized the background regimen.
The study included 23 children, 16 of them (70%) boys, with a median age of 10 (interquartile range 6 to 11). Most children (16) lived in the United States, while 4 lived in South Africa and 3 in Thailand. Half of the children were black, one quarter Hispanic, 17% white, and 13% Asian. Baseline median viral load measured 100,000 copies, while median CD4 count stood at 645 and median CD4 percent at 24%. Children had taken antiretrovirals for a median of 9.3 years. The largest proportion of children were taking a nucleoside, a nonnucleoside, and a protease inhibitor (44%), while 33% were taking nucleosides plus a protease inhibitor, 17% nucleosides plus a nonnucleoside, and 6% only nucleosides.
The researchers dosed dolutegravir at 50 or 70 mg in children weighing more than 40 kg, at 35 mg in children between 30 and 40 kg, at 25 mg in children 20 to 30 kg, and at 20 kg in children under 20 kg. After 48 weeks of treatment, 74% of participants had a viral load below 50 copies and 78% had a load below 400 copies. Median CD4 count rose by about 150 at week 12, by about 200 at week 24, and by about 350 at week 48.
No one stopped their regimen because of adverse events, and no dolutegravir-related adverse event arose during the study. Four children had grade 3 clinical events that the investigators judged unrelated to study drugs (abscess, pneumonia, abnormal behavior, and extremity pain). Three children had a grade 3 lab abnormality unrelated to study drugs.
The study is now evaluating pediatric formulations of dolutegravir in children older than 4 weeks of age.
Reference
1.Wiznia A, Alvero C, Fenton T, et al. IMPAACT 1093: Dolutegravir in 6- to 12-year-old HIV-infected children: 48-week results. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 816.
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Reported by Jules Levin
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