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The MERIT study of maraviroc in antiretroviral-naive patients with R5 HIV-1: 96-week results
Presented by Michael Saag (United States).
J. Heera1, P. Ive2, M. Botes3, E. Dejesus4, H. Mayer1, J. Goodrich1, N. Clumeck5, D.A. Cooper6, S. Walmsley7, C. Craig8, J. Reeves9, E. van der Ryst8, M. Saag10
1Pfizer Global Research and Development, New London, United States, 2Prudence Ive, Johannesburg, South Africa, 3University of Pretoria and Tshwane Academic Division of the National health Laboratory Service, Pretoria, South Africa, 4Orlando Immunology Center, Orlando, United States, 5Saint-Pierre University Hospital, Brussels, Belgium, 6University of New South Wales, Sydney, Australia, 7University of Toronto, Toronto, Canada, 8Pfizer Global Research and Development, Sandwich, United Kingdom, 9Monogram Biosciences, Sount San Francisco, United States, 10University of Alabama at Birmingham Medical Center, Brimingham, United States
Background: MERIT evaluated maraviroc (MVC) versus efavirenz (EFV), both with Combivir (CBV), in antiretroviral-naive patients with R5 HIV-1. A 48-Week retrospective reanalysis of MERIT (MERIT-ES) showed similar virologic responses < 50 copies/mL between arms using an enhanced sensitivity tropism assay (Trofile). We present MERIT and MERIT-ES week 96 efficacy and safety analyses.
Methods: Patients were randomized to EFV 600mg QD or MVC 300mg BID. Patients with non-R5 virus at screening by blinded retesting with the enhanced assay were excluded from the MERIT-ES analysis. Neither the original nor MERIT-ES analyses were powered to determine noninferiority of MVC versus EFV at 96 weeks.
Results: Baseline demographics were similar between groups.
| Week 96 | MERIT (original Trofile) | MERIT-ES (enhanced Trofile reanalysis) | | | MVC
(n=360) | EFV
(n=361) | Difference* (lower bound of 1 sided 97.5% CI?) | MVC
(n=311) | EFV
(n=303) | Difference* (lower bound of 1 sided 97.5% CI) | | <400 copies/mL, % | 61.4 | 64.5 | -3.2
(-10.2) | 64.0 | 64.4 | -0.4
(-7.9) | | HIV-1 RNA <400 copies/mL, % (TLOVR) | 61.7 | 64.3 | -2.7
(-9.7) | 64.3 | 64.0 | 0.2
(-7.3) | | HIV-1 RNA <50 copies/mL, % | 56.9 | 62.6 | -5.8
(-12.8) | 58.8 | 62.7 | -3.9
(-11.5) | | HIV-1 RNA <50 copies/mL, % (TLOVR) | 57.8 | 60.9 | -3.2
(-10.3) | 60.5 | 60.7 | -0.3
(-7.9) | | Median (min, max) change from baseline in CD4+ cell count, cells/mm3 | 224
(-66, 716)
| 195
(-139, 693) | ND | 224
(-66, 716) | 191
(-139, 693) | ND | | Adjusted for randomization strata; † For descriptive purposes only; TLOVR = time to loss of virologic response |
The difference between the TLOVR and primary analyses was due to 11 MVC patients with >50 RNA copies/mL at Week 96, of whom 9 (82%) subsequently resuppressed to < 50 copies/mL.
There were no new or unique safety findings. 56 EFV patients discontinued for adverse events (AEs) versus 22 on MVC. AIDS-defining illnesses, grade 3/4 AEs and malignancies were more common on EFV. Grade 3/4 transaminase abnormalities were similar between groups.
Conclusion: As observed at Week 48, when patients with non-R5 virus at screening by an enhanced tropism assay were retrospectively excluded MVC virologic response was greater than that observed using the original tropism test and similar to that observed in the comparator arm.
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