dian change from baseline in CD4+ cell count at the last measurement up to Week 48 was +89 cells/mm3 in patients receiving APTIVUS/ritonavir in combination with newly introduced enfuvirtide (N=124) and +18 cells/mm3 in the comparator PI/ritonavir (N=96) arm.
14.2 Pediatric Patients
The pharmacokinetic profile, safety and activity of APTIVUS/ritonavir was eva luated in a randomized, open-label, multicenter study. This study enrolled HIV-1 infected, treatment-experienced pediatric patients (with the exception of 3 treatment-naïve patients), with baseline HIV-1 RNA of at least 1500 copies/mL. The age ranged from 2 through 18 years and patients were stratified by age (2 to <6 years, 6 to <12 years and 12 to 18 years). One hundred and ten (110) patients were randomized to receive one of two APTIVUS/ritonavir dose regimens: 375 mg/m2/150 mg/m2 dose (N=55) or 290 mg/m2/115 mg/m2 dose (N=55), plus background therapy of at least two non-protease inhibitor antiretroviral drugs, optimized using baseline genotypic resistance testing. All patients initially received APTIVUS oral solution. Pediatric patients who were 12 years or older and received the maximum dose of 500/200 mg BID could subsequently change to APTIVUS capsules at day 28 [see Adverse Reactions (6.2), Use in Specific Populations (8.4), Clinical Pharmacology (12.3), and Microbiology (12.4)].
Demographics and baseline characteristics were balanced between the APTIVUS/ritonavir dose groups. The 110 randomized pediatric patients had a median age of 11.7 years (range 2 to 18), and were 57.2% male, 68.1% white, 30% black, and 1.8% Asian. The median baseline plasma HIV-1 RNA was 4.7 (range 3.0 to 6.8) log10 copies/mL and median baseline CD4+ cell count was 379 (range 2 to 2578) cells/mm3. Overall, 37.4% of patients had a baseline HIV-1 RNA of >100,000 copies/mL; 28.7% had a baseline CD4+ cell count ≤200 cells/mm3, and 48% had experienced a prior AIDS defining Class C event at baseline. Patients had prior exposure to a median of 4 NRTIs, 1 NNRTI, and 2 PIs.
Eighty three (75%) completed the 48 week period while 25% discontinued prematurely. Of the patients who discontinued prematurely, 9 (8%) discontinued due to virologic failure, and 9 (8%) discontinued due to adverse reactions.
At 48 weeks, 40% of patients had viral load <400 copies/mL. The proportion of patients with viral load <400 copies/mL tended to be greater (70%) in the youngest group of patients, who had less baseline viral resistance, compared to the older groups (37% and 31%). The HIV-1 RNA results are presented in Table 13.
Table 13 Proportion of Patients with HIV-1 RNA <400 copies/mL (<50 copies/mL) by age and dose*
|
APTIVUS/ritonavir Dose Regimen |
2 to <6 years
(N=20) |
6 to <12 years
(N=38) |
12 to 18 years
(N=52) |
|
* The number of baseline tipranavir resistance-associated substitutions were fewer in the 2 to <6 year old patients than the 6 to 18 year old patients enrolled in study 1182.14 |
|
375 mg/m2/150 mg/m2 |
n=10
70% (42%) |
n=19
50% (39%) |
n=26
33% (30%) |
|
290 mg/m2/115 mg/m2 |
n=10
70% (54%) |
n=19
37% (32%) |
n=26
31% (23%) |
The dose selection for all age groups was based on the fol
