520
Tipranavir Achieves Twice the Rate of Treatment Response and Prolongs Durability of Response vs Comparator PI in ART-experienced Patients, Independent of Baseline CD4 Cell Count or Viral Load: Week 48 RESIST 1 and 2 Combined Analyses
Christine Katlama*1, S Walmsley2, C Hicks3, P Cahn4, D Neubacher5, J Villacian5, and for the RESIST Investigators
1Hosp Pitié-Salpétrière, Paris, France; 2Toronto Gen Hosp, Univ of Toronto, Canada; 3Duke Univ Sch of Med, Durham, NC, US; 4Fndn Huésped, Buenos Aires, Argentina; and 5Boehringer Ingelheim Pharma, Ridgefield, CT, US
Background: Tipranavir/ritonavir
(TPV/r), a potent agent against multi-protease inhibitor (PI)-resistant HIV, is
now approved in several countries. We present week-48 treatment responses to
TPV/r or comparator PI/r (CPI/r) regimens in ART-experienced, RESIST 1 and 2
patients, stratified by PI, baseline CD4 cell counts and baseline viral loads.
Methods: RESIST 1 and 2 are randomized, ongoing, open-label
phase III studies of TPV/r (500/200 mg twice daily) or CPI/r, plus optimized background
regimen. Patients had
≥3-class ART experience, ≥2 previous PI-based regimens, ≥1 primary PI mutation, and <3 mutations among 33,
82, 84, and 90. CPI/r and optimized background regimen
were selected pre-randomization. TR rates (confirmed ≥1 log10
copies/mL viral load reduction without treatment
change) at week 48 were determined for PI, baseline CD4 count, and baseline
viral load strata, in a combined analysis.
Results: We randomized 1483 patients: 746 to TPV/r; 737 to CPI/r. Baseline mean CD4
cell counts were 196/195 cells/mm3 and mean viral loads were
4.73/4.73 log10 copies/mL in TPV/r and
CPI/r arms, respectively. Median prior ART were 12. Pre-selected PI were lopinavir (LPV; 722), saquinavir
(SQV; 323), amprenavir (APV; 392), and indinavir (IDV; 46). 20.5% of patients took enfuvirtide (EFV).
Risk
of treatment failure was 34% lower in TPV/r vs CPI/r
patients (p <0.001). Median TTF
was 113 days in TPV/r (IQR 0 to >494) vs 0 in
CPI/r (IQR 0 to 119): TPV/r responses were more durable. Week-48 TR rates were
higher in the TPV/r arm than the CPI/r in all PI (Table 1), baseline viral load
and CD4 strata (Table 2). Treatment response fell in both arms with increased
viral load or lower CD4 count.
Table 1: Week-48 Treatment Response and Baseline Viral
Load (%; n/N) by PI Stratum (ITT NCF)
|
|
TPV/r
|
CPI/r
|
|
|
Treatment response
|
<400 copies/mL
|
<50 copies/mL
|
Treatment response
|
<400 copies /mL
|
<50 copies /mL
|
|
LPV
|
33.0
(120/364)
|
31.0
(113/364)
|
23.9
(87/364)
|
17.0
(61/358)
|
16.8
(60/358)
|
11.5
(41/358)
|
|
IDV
|
34.8
(8/23)
|
30.4
(7/23)
|
17.4
(4/23)
|
4.3
(1/23)
|
4.3
(1/23)
|
4.3
(1/23)
|
|
SQV
|
35.4
(57/161)
|
32.3
(52/161)
|
22.4
(36/161)
|
11.1 (18/162)
|
9.3
(15/162)
|
6.2 (10/162)
|
|
APV
|
33.3
(66/198)
|
27.8
(55/198)
|
21.7
(43/198)
|
17.0 (33/194)
|
13.4
(26/194)
|
11.9
(23/194)
|
Table 2: Week-48 TR rate by CD4 Cell Count and
Viral Load Strata (ITT NCF)
|
|
TPV/r
|
CPI/r
|
|
CD4
(cells/mm3)
|
|
|
|
>350
|
41.3 (45/109)
|
21.8 (27/124)
|
|
>200-350
|
40.9 (76/186)
|
18.4 (33/179)
|
|
50-200
|
33.8 (99/293)
|
16.0 (40/250)
|
|
<50
|
18.4 (28/152)
|
6.3 (11/174)
|
|
VL
(copies /mL)
|
|
|
|
≤10,000
|
54.1 (60/111)
|
33.3 (39/117)
|
|
>10,000-100,000
|
33.5 (119/355)
|
15.7 (52/331)
|
|
>100,000
|
25.7 (72/280)
|
7.6 (22/289)
|
Conclusions:
Week-48 treatment response rates were superior in TPV/r patients
vs CPI/r, regardless of PI/r, baseline viral load or
CD4 cell count. Initiating TPV/r in ART-experienced patients with lower baseline
viral loads or higher baseline CD4 cell counts improved virological
responses.
|
