Pharmacokinetics, Safety and Antiviral Activity of Fosamprenavir/Ritonavir-containing Regimens in HIV-infected Children Aged 4 Weeks to 2 Years-48-week Study Data

作者：Cotton Mark; Cassim Haseena; Pavia Ruz Noris; Garges Harmony P; Perger Teodora; Ford Susan L; Wire Mary Beth; Givens Naomi; Ross Lisa L; Lou Yu; Sievers Joerg; Cheng Katharine^*

来源：Pediatric Infectious Disease Journal, 2014, 33(1): 57-62.

DOI：10.1097/INF.0b013e3182a1123a

• fosamprenavir
• HIV-1
• infants
• children

Background: Pharmacokinetics, safety and antiviral activity of fosamprenavir (FPV) with ritonavir (RTV) twice daily were evaluated in HIV-1-infected infants and children 4 weeks to %26lt;2 years over 48 weeks. %26lt;br%26gt;Methods: Results from intensive pharmacokinetic sampling of subjects enrolled in single dose visits was used to determine individualized dosing for the first 6-10 subjects in each of 2 cohorts (4 weeks to %26lt;6 months, 6 months to %26lt;2 years); steady state pharmacokinetic data were then used to select the dosage regimen for the remaining subjects recruited to the cohort. Intensive pharmacokinetic sampling was performed at week 2 or 8; predose samples were collected every 4-12 weeks thereafter. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks. %26lt;br%26gt;Results: Fifty-nine subjects received study medication. FPV 45 mg/kg boosted with RTV 7 to 10 mg/kg BID achieved average plasma amprenavir area under curve(0-tau) values 26% to 28% lower and Cmax similar to historical adult data for FPV/RTV 700/100 mg BID; amprenavir C tau values were lower in the subjects %26lt;6 months of age. At week 48, 35 of 54 (65%) subjects had achieved plasma HIV-1 RNA %26lt;400 copies/mL and 33 of 54 (61%) had plasma HIV-1 RNA values %26lt;50 copies/mL. The most common adverse events were diarrhea, upper respiratory tract infection, gastroenteritis and otitis media. %26lt;br%26gt;Conclusions: Final FPV/RTV dosing regimens achieved plasma amprenavir exposures comparable with those from regimens approved in adults, with the exception of trough exposures in the %26lt;6-month-old infants. The FPV/RTV regimens led to viral suppression in 61% of patients and were generally well tolerated.