788
48-Week Results from BENCHMRK-1, a Phase III Study of Raltegravir in Patients Failing ART with Triple-class Resistant HIV-1
David Cooper*1, J Gatell2, J Rockstroh3, C Katlama4, P Yeni5, A Lazzarin6, X Xu7, R Isaacs7, H Teppler7, B Y Nguyen7, and the BENCHMRK-1 Study Group
1Univ of New South Wales, Sydney, Australia; 2Univ of Barcelona, Spain; 3Univ of Bonn, Germany; 4Hosp Pitie-Salpetriere, Paris, France; 5Hosp Bichat-Claude Bernard, Paris, France; 6San Raffaele Sci Inst, Milan, Italy; and 7Merck Res Labs, West Point, PA, US
Background: In 3 studies of HIV-infected patients
with limited treatment options, raltegravir (RAL) with optimized background
therapy (OBT) was generally well tolerated and provided superior viral
suppression for ≥24 weeks compared to OBT alone. These are the follow-up
48-week results from BENCHMRK-1 (Protocol 018), an ongoing multi-center, double-blind
phase III study conducted in Europe, Asia/Pacific, and Peru.
Methods: Patients failing ART with triple-class
resistant HIV-1 were randomized 2:1 to oral twice-daily raltegravir (RAL) 400
mg or placebo, both in combination with OBT. Specified efficacy endpoints
included percentage of patients with vRNA levels <400 and <50 copies/mL,
and the mean change from baseline in CD4 cell counts.
Results: Of 352 patients randomized, 350
received ≥1 dose of study drug. Baseline characteristics were comparable
between the RAL and placebo groups. At baseline, median CD4 counts were 140 and
105 cells/mm3, and geometric mean viral loads were 4.6 and 4.5 log10
copies/mL in the RAL and placebo groups, respectively. OBT contained <1
active drug (genotypic sensitivity score of 0) in 30% and 29% of patients in
the RAL and placebo groups, respectively. RAL was generally well tolerated over
48 weeks. Planned 48-week efficacy analyses are shown below, along with the
24-week results:
|
|
% Patients (95%CI) with HIV RNA <400 copies/mL2
|
% Patients (95%CI) with HIV RNA <50 copies/mL2
|
Change from baseline in CD4 cells/ mm3
[++]
|
|
|
Week 24
|
Week 48
|
Week 24
|
Week 48
|
Week 24
|
Week 48
|
|
RAL§ (n = 232)
|
75
(69 to 81)
|
74
(67 to 79)
|
60
(54 to 67)
|
65
(58 to 71)
|
87
(74 to 99)
|
120
(102 to 138)
|
|
PBO§ (n = 118)
|
39
(30 to 48)
|
36
(28 to 46)
|
33
(25 to 42)
|
31
(23 to 41)
|
35
(23 to 48)
|
49
(30 to 69)
|
|
RAL – PBO1
|
36
(26 to 46)*
|
37
(26, to 47)*
|
27
(16 to 37)*
|
33
(22 to 43)*
|
52
(34 to 69)*
|
71
(45 to 97)*
|
|
§ RAL and PBO were given with OBT
1
Difference between RAL and PBO; a positive value favors RAL over PBO
2
Non-Completer=Failure
[++]Baseline values carried forward for
virologic failures
*Nominal P<0.001
|
Conclusions: In this pivotal study of pts failing
ART with triple-class resistant HIV, RAL + OBT demonstrated superior
antiretroviral and immunological responses compared to OBT alone, that were
sustained out to 48 weeks.
|
