571b 
96-Week Results from BENCHMRK 1 and 2, Phase III Studies of Raltegravir in Patients Failing ART with Triple-class-resistant HIV
Roy Steigbigel*1, D Cooper2, J Eron3, J Gatell4, P Kumar5, J Rockstroh6, H Wan7, P Sklar7, H Teppler7, B-Y Nguyen7, and BENCHMRK-1 and 2 Study Groups
1State Univ of New York at Stony Brook, US; 2Univ of New South Wales, Sydney, Australia; 3Univ of North Carolina at Chapel Hill, US; 4Univ of Barcelona, Spain; 5Georgetown Univ Med Ctr, Washington, DC, US; 6Univ of Bonn, Germany; and 7Merck Res Labs, West Point, PA, US
Background: In studies of HIV-infected patients
with limited treatment options, raltegravir (RAL) combined with optimized
background therapy (OBT) was generally well tolerated and provided superior
viral suppression for 48 weeks compared to OBT alone. Here we present the 96-week
results from BENCHMRK 1 and 2 (protocols 018 and 019), ongoing, double-blind
phase III studies being conducted globally.
Methods: Patients failing ART with triple-class
resistant HIV were randomized 2:1 to oral twice-daily RAL (400 mg) or placebo
(PBO). All patients received OBT. Pre-specified efficacy endpoints included percentage
of patients with HIV RNA levels <50 copies/mL and the mean change in CD4
cell counts from baseline.
Results: Baseline characteristics in the
combined studies were similar in the RAL and PBO groups. At baseline, median
CD4 counts were 119 and 123 cells/mm3, and geometric mean viral
loads were 4.6 and 4.6 log10 copies/mL in the RAL and PBO groups,
respectively. Genotyping demonstrated that OBT contained <1 active drug
(sensitivity score = 0) in 25% and 28% of patients in the RAL and PBO groups,
respectively. RAL was generally well tolerated with few discontinuations (18 patients;
3.9%) due to adverse events. Results from the 96-week combined efficacy analyses
are shown below along with 24-week and 48-week results:
|
|
% patients (95%CI) with HIV RNA <50 copies/mL2
|
Change from baseline3
CD4 cells/mm3
|
|
|
24 weeks
|
48 weeks
|
96 weeks
|
24 weeks
|
48 weeks
|
96 weeks
|
|
RAL
(n = 462)
|
63
(58, 67)
|
62
(58, 67)
|
58
(52, 62)
|
83
( 75, 92)
|
109
( 97, 120)
|
123
( 109, 137)
|
|
PBO
(n = 237)
|
34
(28, 40)
|
33
(27, 39)
|
26
(21, 32)
|
36
( 27, 46)
|
45
( 32, 57)
|
49
( 35, 63)
|
|
Difference between RAL and PBO1
|
29*
(21, 36)
|
29*
(22, 36)
|
31*
(23, 38)
|
47*
( 34, 60)
|
64*
( 47, 81)
|
74*
( 55, 94)
|
|
1
RAL and PBO were given with OBT. A positive value favors RAL over PBO;
*Nominal p <0.001.
2
Non-completer = failure
3 Baseline values carried forward for virologic
failures
|
Conclusions: In these pivotal studies of patients
failing ART with triple-class resistant HIV, RAL plus OBT demonstrated superior
antiretroviral and immunological responses compared to OBT alone, that were
sustained as long as 96 weeks.
|
