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Efficacy of Raltegravir, an HIV Integrase Inhibitor, in Combination with Regimens Containing Enfuvirtide, Darunavir, or Tipranavir in Patients with Triple-class Resistant Virus: Combined Results from BENCHMRK-1 and BENCHMRK-2
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Reported by Jules Levin
11th European AIDS Conference, Madrid, Oc3 23-27, 2007
P.N. Kumar,1 D.A. Cooper,2 R.T. Steigbigel,3 J. Zhao,4 H. Teppler,4
B-Y. Nguyen4 for the BENCHMRK-1 and BENCHMRK-2 Study Groups
1Georgetown University Medical Center, Washington, DC, USA; 2National Centre in HIV Epidemiology and Clinical Research, University of
New South Wales, Sydney, Australia; 3State University of New York at Stony Brook, NY, USA; 4Merck Research Laboratories, PA, USA
AUTHOR CONCLUSIONS
In HIV-1-infected patients failing antiretroviral therapy with triple-class resistant HIV, raltegravir 400 mg BID plus OBT at Week 24
- Has rapid, potent, and superior antiretroviral and immunological efficacy compared to placebo plus OBT
- In patients receiving new, active antiretroviral therapies in OBT, ≥68% of patients achieved HIV RNA <50 copies/mL
- The treatment effect of raltegravir is consistent regardless of GSS or use of selected ARTs in OBT
ABSTRACT
Background: BENCHMRK-1 and BENCHMRK-2 are ongoing international, randomized, double-blind studies of oral raltegravir 400 mg b.i.d. vs. placebo (2:1 randomization), each with optimized background therapy (OBT), in HIVinfected
patients failing anti-retroviral therapies (ARTs) with HIV resistant to 3 classes of oral ARTs.
Methods: Data from both studies were combined for analysis. Efficacy endpoints
included % of patients with HIV RNA <400 and <50 copies/mL and change from
baseline in CD4 cell counts at Week 16. Subgroup analyses assessed the efficacy of raltegravir when added to regimens containing first-use of enfuvirtide (ENF) or darunavir (DRV), or tipranavir (TPV) in patients with virus sensitive to TPV by genotypic (GT-sensitive) or phenotypic (PT-sensitive) resistance testing.
Results: Primary analysis (Week 16) results are displayed. Week 24 data from ABOUT 60% of patients also demonstrated superior efficacy of raltegravir over placebo.
Note: (nv) indicates use in patients naive to that drug.
Raltegravir in combination with OBT was generally well tolerated.
Conclusions: The combined results of BENCHMRK-1 and BENCHMRK-2 confirm that raltegravir 400 mg b.i.d. plus OBT demonstrates potent and superior antiretroviral effect compared to placebo plus OBT in patients with triple-class resistant HIV. The best overall treatment responses were observed when raltegravir was used with either 1 or 2 new active ARTs.
INTRODUCTION
· Raltegravir + OBT demonstrated potent and superior antiretroviral activity compared to placebo + OBT in BENCHMRK-1 and BENCHMRK-2 at Week
161,2
- Partial data at Week 24 showed similar response
- When raltegravir was combined with enfuvirtide and/or darunavir, >90% of patients achieved HIV RNA <400 copies/mL
· This presentation provides complete Week 24 data, which confirm previously reported Week 16 data
· Since both studies are identical in design, integrated analyses of efficacy were performed using combined Week 24 data
- to confirm the superior efficacy of raltegravir
- to demonstrate the consistent treatment effect of raltegravir in different subgroups
METHODS
BENCHMRK-1 & -2 Study Design
Randomized, double-blind, placebo-controlled with Data and Safety Monitoring
Board
Selected investigational antiretrovirals, darunavir and tipranavir, permitted in OBT
BENCHMRK-1 & -2 Combined Analyses
Efficacy Endpoints:
- Percent of patients with HIV-1 RNA <400 copies/mL
- Percent of patients with HIV-1 RNA <50 copies/mL
- Change from baseline in CD4 cell count
Subgroup Analyses by:
- Use of selected ARTs including enfuvirtide (ENF), darunavir (DRV), or tipranavir
(TPV)
- Genotypic sensitivity score (GSS):
· "Active" drug in the OBT defi ned by results of PhenosenseGT testing at
baseline
· For each "active" drug in OBT, +1 added to score
· For enfuvirtide, +1 added to score for use in ENF-naive patients
· For darunavir, +1 added to score for use in DRV-naive patients
RESULTS
Figure 1. BENCHMRK-1 & -2 Combined Efficacy
(Complete Week 24 Data)
--75% taking raltegravir plus OBT vs 40% taking placebo plus OBT achieved <400 c/ml.
--63% taking raltegravir vs 34% taking placebo achieved <50 c/ml.
--cd4 increase was average of 84 cells from baseline for raltegrsavir vs 37 cells for placebo.
P<0.001 for all 3 of these.
Note: (nv) indicates use in patients naive to that drug.
For percent < 400 and <50 copies/mL, virologic failures were carried forward.
For mean CD4 changes, baseline-carry-forward was used for virologic failures.
References:
1. Cooper DA; Gatell J; Rockstroh J; Katlama C; Yeni P; Lazzarin A; Chen J; Isaacs R; Teppler H; Nguyen B-Y for the BENCHMRK-1 Study Group. Results of BENCHMRK-1, a Phase III Study Evaluating the Effi cacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus (abstract 105aLB). Presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Feb 25-28, 2007.
2. Steigbigel R, Kumar P, Eron J, Schechter M, Markowitz M, Loutfy M, Zhao J, Isaacs R, Nguyen B-Y, Teppler H for the BENCHMRK-2 Study Group. Results of BENCHMRK-2, a Phase III Study Evaluating the Effi cacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus (abstract 105bLB). Presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Feb 25-28, 2007.
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