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Safety and Antiviral Activity of Fosamprenavir-containing Regmens in HIV-infected 2- to 18-Year-Old Pediatric Subjects (Interim Data, Study APV29005)
Coleen Cunningham*1, A Freedman2, S Read3, D Duiculescu4, E Voronin5, I De Jose6, D Perez-Tamarit7, A Carrod8, J Yeo8, and H Garges9
1Duke Univ Med Ctr, Durham, NC, US; 2New York Weill Cornell Med Ctr, NY US; 3Hosp for Sick Children, Toronto, Canada; 4Spitalul Clin de Boli Infectioase si Tropicale “Victor Babes”, Bucharest, Romania; 5St Petersburg Republic Hosp of Infectious Disease, Russia; 6Hosp Infantil la Paz, Madrid, Spain; 7Hosp Infantil la Fe, Valencia, Spain; 8GlaxoSmithKline, Greenford, UK; and 9GlaxoSmithKline, Research Triangle Park, NC, US
Background: The HIV-1 protease inhibitor (PI) fosamprenavir
(fAPV), the phosphate-ester prodrug
of amprenavir (APV), 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
alone or with ritonavir (RTV) twice daily. Pharmacokinetics
data will be presented at a later time.
Methods: This was a prospective, open-label, multi-center,
48-week cohort study with interim analysis (cut-off date May 22, 2006). Formal
statistical hypothesis testing was not performed in this non-comparative
study.
Results: We enrolled 75 HIV-1-infected subjects and received
at least 1 dose of fAPV (±RTV). Median exposure to fAPV was 52 weeks (range 2 to 84 weeks), with 68% exposed
>48 weeks. Abacavir (ABC)/lamivudine
(3TC) was the most common initial background ART (used
by 45%). Of the total, 21 subjects were aged 2 to 5 years, 25 were aged 6 to 11
years, and 29 were aged 12 to 18 years. A majority of subjects were female (57%)
and white (69%). At baseline, 45 of 75 were PI-naïve and 30 of 75 were PI-experienced.
Only PI-naïve 2- to 5-year-old subjects received unboosted fAPV
twice daily (18 of 75); all other subjects received fAPV/RTV
twice daily (57 of 75). Median baseline HIV-1 RNA was 5.1 log10
copies/mL for the fAPV
group, and 4.5 log10 copies/mL and
4.6 log10 copies/mL in the fAPV/RTV group, for PI-naive and PI-experienced subjects,
respectively. Of the 75 subjects, 12 (16%) discontinued their treatment
regimen prematurely, 2 from the fAPV group and 10
from the fAPV/RTV group. HIV-1 RNA <400 copies/mL among PI-naïve subjects at week 24 was 67% in the fAPV group, and 70% in the fAPV/RTV
group vs 57% of PI-experienced subjects in the fAPV/RTV group (intent-to-treat-experienced, TLOVR). Median
increases in CD4+ cell percentages at week 24 occurred in all
groups, and ranged from 4 to 8%. Drug-related grade 2-4 adverse events occurred
in 9 of the 75 (12%); the most frequent were diarrhea (2 of 75, 3%) and
vomiting (2 of 75, 3%); 9 subjects experienced severe adverse events; including
6 with hypersensitivity to ABC. The incidence of treatment-emergent grade 3/4
clinical chemistry and hematology laboratory abnormalities was 6% (1 of 18) in
the fAPV group and 14% (8 of 57) in the fAPV/RTV group.
Conclusions: Following a median duration of 52 weeks
exposure fAPV and fAPV/RTV were
generally well tolerated and demonstrated good antiviral activity in both PI-naïve
and PI-experienced 2- to 18-year-old pediatric subjects.
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