789 
48-Week Results from BENCHMRK-2, a Phase III Study of Raltegravir in Patients Failing ART with Triple-class Resistant HIV
Roy Steigbigel*1, P Kumar2, J Eron3, M Schechter4, M Markowitz5, M Loutfy6, J Zhao7, R Isaacs6, B Y Nguyen7, H Teppler7, and the BENCHMRK-2 Study Group
1State Univ of New York at Stony Brook, US; 2Georgetown Univ Med Ctr, Washington, DC, US; 3Univ North Carolina at Chapel Hill, US; 4Federal Univ of Rio de Janeiro, Brazil; 5Aaron Diamond AIDS Res Ctr, The Rockefeller Univ, New York, NY, US; 6Univ of Toronto, Canada; and 7Merck Res Labs, West Point, PA, US
Background: In 3 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 ≥24 weeks compared to OBT alone. Here we present
the 48-week results from BENCHMRK-2 (Protocol 019), an ongoing double-blind
phase III study being conducted in North and South America.
Methods: Patients failing ART with triple-class
resistant HIV were randomized 2:1 to oral twice-daily RAL 400 mg or placebo.
All patients received OBT. Prespecified efficacy endpoints included percentage
of patients with HIV RNA levels <400 and <50 copies/mL, and the mean
change in CD4 cell counts from baseline.
Results: Baseline characteristics were similar in
the RAL and placebo groups. At baseline, median CD4 counts were 102 and 132
cells/mm3, and geometric mean viral loads were 4.7 and 4.7 log10
copies/mL in the RAL and placebo groups, respectively. Genotyping demonstrated
that OBT contained <1 active drug (sensitivity score = 0) in 20% and 27% of
patients in the RAL and placebo groups, respectively. RAL was generally well
tolerated over 48 weeks. Preplanned 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 CD4 cells/ cubic mm11
|
|
Week 24
|
Week 48
|
Week 24
|
Week 48
|
Week 24
|
Week 48
|
|
RAL
(n = 230)
|
75
(69 to 81)
|
71
(65 to 77)
|
65
(59 to 71)
|
60
(53 to 66)
|
81 (69 to 94)
|
98
(84 to 113)
|
|
Placebo (n = 119)
|
41
(32 to 51)
|
38
(29 to 47)
|
35
(26 to 44)
|
35
(26 to 44)
|
37 (23 to 51)
|
40
(24 to 56)
|
|
RAL -PBO1
|
34
(23 to 44)*
|
33
(22 to 43)*
|
31
(20 to 41)*
|
25
(14 to 35)*
|
44
(25 to 63)*
|
59
(37 to 80)*
|
|
RAL and placebo were given with OBT
1
Difference between RAL and placebo; a positive value favors RAL over placebo
2
Non-Completer = Failure
11
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 plus OBT maintained superior
antiretroviral and immunological responses compared to OBT alone for at least
48 weeks.
|
