Pharmacokinetics and 48-week safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2- to 18-year-old children

• Published in: The Pediatric infectious disease journal Vol. 33; no. 1; p. 50
• Main Authors: Fortuny, Claudia, Duiculescu, Dan, Cheng, Katharine, Garges, Harmony P, Cotton, Mark, Tamarirt, Desamparados Pérez, Ford, Susan L, Wire, Mary Beth, Givens, Naomi, Ross, Lisa L, Lou, Yu, Perger, Teodora, Sievers, Jörg
• Format: Journal Article
• Language: English
• Published: United States 01.01.2014
• Subjects: Adolescent; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Carbamates - administration & dosage; Carbamates - adverse effects; Carbamates - blood; Carbamates - pharmacokinetics; CD4 Lymphocyte Count; Child; Child, Preschool; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Male; Organophosphates - administration & dosage; Organophosphates - adverse effects; Organophosphates - blood; Organophosphates - pharmacokinetics; Ritonavir - administration & dosage; RNA, Viral - blood; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - blood; Sulfonamides - pharmacokinetics; Viral Load
• ISSN: 1532-0987
• DOI: 10.1097/INF.0b013e3182a1126a

Pharmacokinetics, safety and antiviral activity of twice-daily fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor-naïve and -experienced HIV-1-infected children. 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. Twenty protease inhibitor-naïve 2- to <6-year-old subjects received antiretroviral treatment including unboosted fosamprenavir twice-daily, whereas 89 protease inhibitor-naïve 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; 8%) and fosamprenavir/ritonavir group (190 cells/mm; 8%). The most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity. 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.