Impact
of Prior PI Usage on Week 48 Responses to Tipranavir Boosted with Ritonavir  The
Phase
III RESIST trials demonstrated that TPV/r
was significantly more effective than an optimized comparator PI/r (CPI/r). This
analysis assessed the impact of previous PI use on various outcomes at 48 weeks.
RESIST patients had >/=3-class ARV experience, including >=2 PI-based
regimens; any CD4 cell count; viral load (VL) >/=1000 copies/mL; and HIV isolates
carrying >/= 1 primary PI mutation and </=2 mutations at 33, 82, 84, 90.
Patients were randomized to receive TPV/r (500 mg/200 mg BID) or pre-selected
CPI/r plus optimized background regimen. Treatment response (TR) was defined as
a confirmed >/= 1 log10 copies/mL decrease in VL from baseline without treatment
change.
Results
1483 patients were randomized: 746 TPV/r; 737 CPI/r. Baseline mean CD4 cell counts:
196/195 cells/mm3;
mean VLs: 4.73/4.73 log10 copies/mL in TPV/r and CPI/r arms respectively.
Greater proportions of patients in the TPV/r arm had a TR or VL <400 or <50
copies/mL than control patients.
With increased PI experience, responses to CPI/r were impaired to a greater extent
than those to TPV/r.
|
|
TPV/r |
CPI/r |
|
Prior PIs* |
TR
(%) |
%
<400 cp/mL |
%
<50 cp/mL |
TR
(%) |
%
<400 cp/mL |
%
<50 cp/mL |
| 2 |
42.5
(34/80) |
41.3
(33/80) |
35.0
(28/80) |
34.3
(24/70) |
32.9
(23/70) |
24.3
(17/70) |
| 3 |
37.9
(50/132) |
35.6
(47/132) |
28.0
(37/132) |
25.9
(38/147) |
24.5
(36/147) |
21.8
(32/147) |
| 4 |
33.5
(73/218) |
31.2
(68/218) |
22.0
(48/218) |
9.8
(18/184) |
9.8
(18/184) |
4.9
(9/184) |
| 5 |
29.8
(57/191) |
22.5
(43/191) |
15.7
(30/191) |
10.0
(21/209) |
7.2
(15/209) |
4.8
(10/209) |
| 6 |
28.4
(29/102) |
26.5
(27/102) |
17.6
(18/102) |
5.0
(5/100) |
4.0
(4/100) |
2.0
(2/100) |
|
*
data from the few patients who had taken 1 or >7 PIs omitted |
In conclusion,
the authors write, "At all levels of PI experience, TPV/r provided superior
treatment efficacy over CPI/r at 48 weeks. This difference increased with increasing
PI experience.
"Patients
who started TPV/r with limited (<3) PI experience, and able to take active
background ARVs, had better treatment outcomes at Week 48 than those with greater
PI experience." University
of California, Davis, Sacramento, United States, University Hospital Frankfurt,
Frankfurt, Germany, McGill University Health Center, Montreal, Canada, Boehringer
Ingelheim Pharmaceuticals, Inc., Ridgefield, United States. 08/18/06 Reference
R
B Pollard, S Staszewski, R LeBlanc, and others. Impact of prior PI usage on week
48 responses to tipranavir boosted with ritonavir (TPV/r). 16th International
AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract TUPE0067.
|
