Pharmacokinetics and 48-week Safety and Antiviral Activity of Fosamprenavir-containing Regimens in HIV-infected 2-to 18-year-old Children

Fecha de publicación: 01/01/2014

Autores de IIS La Fe

Desamparados Perez Tamarit

Autor

Participantes ajenos a IIS La Fe

Fortuny C
Duiculescu D
Cheng K
Garges HP
Cotton M
Ford SL
Wire MB
Givens N
Ross LL
Lou Y
Perger T
Sievers J

Abstract

Background: Pharmacokinetics, safety and antiviral activity of twice-daily fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor-naive and -experienced HIV-1-infected children. Methods: Serial pharmacokinetic samples were collected at week 2 and predose samples every 4-12 weeks. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks. Results: Twenty protease inhibitor-naive 2- to <6-year-old subjects received antiretroviral treatment including unboosted fosamprenavir twice-daily, whereas 89 protease inhibitor-naive and -experienced 2- to 18-year-old subjects received fosamprenavir/ritonavir-containing therapy twice-daily. Median fosamprenavir exposure was 891 days (range 15-1805 days), with 88% exposed >48 weeks. Twice-daily doses of fosamprenavir/ritonavir 23/3 mg/kg in 2- to <6-year olds, 18/3 mg/kg in >= 6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while fosamprenavir 30 mg/kg twice-daily in 2- to <6-year olds led to exposures higher than 1400 mg twice-daily in adults. The proportion of subjects with HIV-1 RNA <400 copies/mL at week 48 was 60% for fosamprenavir and 53-74% for fosamprenavir/ritonavir (intent-to-treat [exposed], snapshot analysis). Median increases in absolute and relative (percentage) CD4 counts from baseline to week 48 occurred in both the fosamprenavir (340 cells/mm(3); 8%) and fosamprenavir/ritonavir group (190 cells/mm(3); 8%). The most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity. Conclusions: Fosamprenavir regimens administered to HIV-1-infected children aged 2-18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable with or higher than adults.