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A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]), for the treatment of antiretroviral naive subjects infected with R5 HIV-1: week 48 results of the MERIT study
Presented by Michael Saag, United States.
Michael Saag1,
Prudence Ive2, Jayvant Heera3, Margaret Tawadrous3,
Edwin DeJesus4, Nathan Clumeck5, David Cooper6,
Andrej Horban7, Lerato Mohapi8, Horacio Mingrone9,
Gustavo Reyes-Teran10, Sharon Walmsley11, Frances Hackman12,
Elna van der Ryst12, Howard Mayer3
1University of Alabama at Birmingham, Birmingham, USA,
2University of the Witwatersrand, Clinical HIV Research
Unit (CHRU), Johannesburg, South Africa,
3Pfizer Global Research and Development, New London, USA,
4Orlando Immunology Center, Orlando, Florida, USA,
5Saint-Pierre University Hospital, Infectious Diseases, Brussels, Belgium,
6University of New South Wales, National Centre in HIV
Epidemiology and Clinical Research, Sydney, Australia,
7Hospital of Infectious Diseases, Warsaw, Poland,
8University of the Witwatersrand, Perinatal HIV
Research Unit, Johannesburg, South Africa,
9HIV Outpatient Care Unit, Muñiz Hospital, Buenos Aires City, Argentina,
10Instituto Nacional de Enfermedades Respiratorias,
Center for Research in Infectious Diseases, Tlalpan, Mexico,
11University of Toronto, Ontario, Canada,
12Pfizer Global Research and Development, Sandwich, UK
Objectives: To compare the safety and efficacy of maraviroc (MVC) versus efavirenz (EFV), both
administered with Combivir (CBV) in antiretroviral-naive patients.
Methods: Patients with only R5 HIV-1, HIV RNA
≥2,000 copies/mL and no EFV, ZDV, or 3TC resistance were randomized to
CBV plus EFV 600mg QD or MVC 300mg QD or BID. The
primary endpoint was percentage of patients with HIV-1-RNA <400 and <50 copies/mL at week 48;
noninferiority of MVC vs EFV was analyzed. The MVC-QD arm was discontinued in
January 2006.
Results:Overall 721 (29% female) patients received ≥1 dose of
study drug and were included in the analysis. Baseline median CD4+ count (241
and 254 cells/mm3) and mean HIV-1 RNA (4.9 and 4.9 log10
copies/mL) were similar in the MVC-BID and EFV arms, respectively. More
patients discontinued from MVC-BID for lack of efficacy compared with EFV
(11.9% versus 4.2%), whereas fewer patients discontinued MVC-BID due to adverse
events (4.1% versus 13.6%). Key efficacy and safety endpoints are shown in the
following table:
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Week 48 results FAS, As Treated
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MVC BID + CBV (N=360)
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EFV + CBV (N=361)
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Difference* (lower bound of 1-sided 97.5% CI)
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HIV RNA <400 copies/mL, %
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70.6
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73.1
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-3.0
(-9.5)
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HIV RNA <50 copies/mL, %
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65.3
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69.3
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-4.2 (-10.9)
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Mean Change from BL in CD4+ count, cells/mm3
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170
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143
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26
(7–46†)
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Patients with Category C Events
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6 (1.7)
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12 (3.3)
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N/A
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*adjusted for randomization strata;
†95% CI
Grade 3/4 AEs were reported by more
patients on EFV compared with MVC-BID. Fewer malignancies occurred on MVC. The
incidence of grade 3/4 transaminase abnormalities was similar between the two
groups.
Conclusions: Non-inferiority
of MVC-BID could be concluded for the <400 but not the <50 copies/mL
endpoint. CD4 cell count increase for MVC-BID was greater than for EFV. MVC-BID
was better tolerated than EFV with fewer discontinuations due to AEs, Category
C events and grade 3/4 adverse events.
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