Background:  The HIV-1 protease inhibitor (PI) fosamprenavir (fAPV) is being studied in PI-naive and experienced HIV-1-infected pediatric subjects ages 2 to 18 years to determine the pharmacokinetics, safety, and antiviral activity of fAPV boosted with ritonavir (fAPV/RTV) once daily. Pharmacokinetic data will be presented at a later time.

Methods:  Prospective, open-label, multi-center, 48-week cohort study. Formal statistical hypothesis testing was not performed in this non-comparative study (cut-off date February 16, 2005). All subjects began the study taking fAPV/RTV once daily. Subjects were allowed to switch to a fAPV/RTV twice-daily regimen after data in PI-experienced adults demonstrated improved responses with twice-daily dosing.

Results:  We enrolled 69 HIV-1-infected subjects who received at least 1 dose of fAPV/RTV. At baseline, 32 of 69 were PI-naïve and 37 of 69 were PI-experienced; 17 subjects were aged 2 to 5 years, 17 were 6 to 11 years, and 35 were 12 to 18 years; 57% of subjects were female; and 51% were white. Median baseline HIV-1 RNA was 4.7 log₁₀ copies/mL for PI-naïve and 4.9 log₁₀ copies/mL for PI-experienced subjects. Abacavir (ABC)/lamivudine (3TC) was the most common initial background ART (46%). In all, 10 subjects, 4 PI-naïve and 6 PI-experienced, subjects switched from fAPV/RTV once daily to twice daily with a median time to switch of 45 weeks (range16 to 103 weeks). Overall, median exposure to fAPV/RTV was 72 weeks (range 0 to 134 weeks) with 70% exposed >48 weeks. Of 69 subjects, 30 (43%) discontinued their treatment regimen prematurely because of adverse effects (n = 10), viral non-response (n = 5), or other reasons (n = 15). HIV-1 RNA <400 copies/mL (ITT[E],TLOVR) among PI-naïve and -experienced subjects at weeks 24/48 was 66%/47% and 57%/43%, respectively. Median increase in CD4⁺ cell percentages at week 48 were 10% for PI-naive and 5% for PI-experienced subjects. Drug-related grade 2-4 adverse events occurred in 19 of 69 (28%); the most frequent were vomiting (5, 7%), diarrhea (3, 4%), and nausea (3, 4%). Of 14 subjects who experienced severe adverse evnts, 3 were drug-related. The most common severe adverse event was hypersensitivity to abacavir (n = 3), followed by pyrexia (n = 2). The incidences of treatment-emergent grade 3/4 clinical chemistry and hematology abnormalities were 6 of 66 (9%) and 14 of 66 (21%), respectively. Neutropenia accounted for 13 of 14 grade 3/4 hematology abnormalities, and was confounded by concomitant medications and sample degradation.

Conclusions:  Following a median duration of 72 weeks’ exposure, the fAPV/RTV regimen was generally well tolerated and demonstrated antiviral activity in PI-naïve and PI-experienced 2- to 18-year-old pediatric subjects.