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96-Week Results from BENCHMRK 1&2, Phase III Studies of Raltegravir (RAL)
in Patients (pts) Failing Antiretroviral Therapy (ART) with Triple-Class Resistant HIV
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Reported by Jules Levin
CROI 209 Feb 8-12 2009, Montreal, Canada
R. T. Steigbigel1, D. A. Cooper2, J. E. Eron3, J. M. Gatell4, P. N. Kumar5, J. K. Rockstroh6, H. Wan7, P. Sklar7, H. Teppler7, B-Y. Nguyen7 for the BENCHMRK-1 and 2 Study Groups
1SUNY at Stony Brook, USA; 2University of New South Wales, Sydney, Australia; 3University of North Carolina, USA; 4University of Barcelona, Spain;
5Georgetown University Medical Center, Washington, DC, USA; 6University of Bonn, Germany; 7Merck Research Laboratories, West Point, PA, USA
CONCLUSIONS
In HIV-infected, treatment-experienced patients failing antiretroviral therapy with triple-class resistant HIV:
Raltegravir 400 mg b.i.d. plus OBT, compared to placebo plus OBT, had potent, superior, and durable antiretroviral and immunological effi cacy sustained through Week 96.
-- 57% of patients receiving raltegravir maintained HIV RNA < 50 copies /mL --
up to 79% in patients receiving new, active ART in OBT
Virologic failure was generally associated with mutations at one of three primary residues, Q148, N155, or Y143, in combination with at least one other mutation.
Rates of ADC and death during double-blind phase were lower for raltegravir than placebo at Week 96, regardless of endpoint, although these differences did not reach statistical significance.
Raltegravir 400 mg b.i.d. plus OBT was generally well tolerated as compared to placebo in combination with OBT.
-- Few adverse experiences led to discontinuation
-- Risk of developing malignancy was comparable between raltegravir and comparator groups.
ABSTRACT
Background: In 3 studies of HIV-infected pts with limited treatment options, RAL combined with optimized background therapy (OBT) was generally well tolerated and provided superior viral suppression for 48 weeks (wk) compared to OBT alone. Here we present the 96-wk results from BENCHMRK 1&2 (Protocols
018&019), ongoing, double-blind Phase III studies being conducted globally.
Methods: Pts failing ART with triple-class resistant HIV were randomized 2:1 to oral BID RAL 400 mg or placebo (PBO). All pts received OBT. Prespecifi ed effi cacy endpoints included % pts with HIV RNA levels <50 copies/mL and the mean change in CD4 cell counts from baseline.
Results (updated): 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 4.7 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 pts in the RAL and PBO groups, respectively. Results from the 96-wk combined efficacy analyses are shown below along with 24-wk and 48-wk results:
RAL and PBO were given with OBT; Difference between RAL and PBO; a positive value favors RAL over PBO;
*Nominal P<0.001; Non-Completer=Failure; Baseline values carried forward for virologic failures RAL was generally well tolerated with few discontinuations [4% (18 pts)] due to adverse events.
Conclusions: In these pivotal studies of pts failing ART with triple-class resistant HIV, RAL plus OBT demonstrated superior antiretroviral and immunological responses compared to OBT alone, that were sustained out to 96 wks.
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