TUAB0101 - Oral Abstract
Maraviroc (MVC) dosed once daily with darunavir/ritonavir (DRV/r) in a 2 drug-regimen compared to emtricitabine/tenofovir (TDF/FTC) with DRV/r; 48-week results from MODERN (Study A4001095)
Presented by Eric Le Fevre (United Kingdom).
H.-J. Stellbrink1, P. Pulik2, J. Szlavik3, D. Murphy4, A. Lazzarin5, J. Portilla6, A. Rinehart7, E. Le Fevre8, A. Fang9, S. Valluri9, G. Mukwaya10, J. Heera11
1ICH-Study Center, Hamburg, Germany, 2SPZOZ Wojewodzki Szpital Zakazny, Warsaw, Poland, 3Egyesittet Szent Istvan es Szent Laszio Korhaz-Rendelointezet, Budapest, Hungary, 4Clinique Medicale L'Actuel, Montreal, Canada, 5Ospedale San Raffaele, Divisione di Malattie Infettive, Milan, Italy, 6Hospital General Universitario de Alicante, Unidad de VIH, Alicante, Spain, 7ViiV Healthcare, Research Triangle Park, United States, 8ViiV Healthcare, Brentford, United Kingdom, 9Pfizer Inc., New York, United States, 10Pfizer Inc., Medicines Development Group, New York, United States, 11Pfizer Inc., Groton, United States
Background: Maraviroc, a CCR5 receptor antagonist, has shown durable antiviral response with a favorable safety profile. Nucleos(t)ide-sparing, 2-drug regimens containing ritonavir-boosted protease inhibitors have not been extensively studied in antiretroviral-naïve subjects. Such regimens may decrease pill burden, toxicities, costs and drug-drug interactions.
Methods: In this multicenter, double-blind, Phase III study, HIV-1 infected antiretroviral-naïve adults with HIV-1 RNA >1000 copies/mL, without reported viral resistance, underwent 2-stage randomization. At screening, subjects were first randomized 1:1 to either genotype (Siemens) or Enhanced Sensitivity Trofile Assay (ESTA, Monogram BioSciences) to identify CCR5-tropic HIV-1 infection. Subjects with CCR5-tropic HIV-1 were then randomized 1:1 to receive MVC 150 mg QD or TDF/FTC 200/300 mg QD each with DRV/r 800/100 mg QD for up to 96 weeks. The primary endpoint was proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 (FDA “snapshot” algorithm).
Results: 797 subjects were dosed (MVC n=396, TDF/FTC n=401). At baseline: median age 37.1 years, 8.8% female, 18.7% non-white, 20.6% HIV-1 RNA >100,000 copies/mL. Proportion of subjects meeting the primary endpoint was 77.3% for MVC and 87.0% for TDF/FTC (difference -9.73%; 95% CI; -15.0% to -4.4%). MVC did not meet the -10% non-inferiority criteria. The difference in the proportion of subjects meeting the primary endpoint between the tropism assays (genotype or ESTA) was not statistically significant (MVC: difference 6.86% in favor of genotyping, 95% CI -1.28% to 15.0%; TDF/FTC: difference 0.3%, 95% CI: -6.4% to 6.9%). More MVC subjects discontinued for lack of efficacy (8.3% vs 2.0%). Protocol defined treatment failure (PDTFs) were 10.1% for MVC and 3.2% for TDF/FTC.
Discontinuations due to AEs were 4.8% for MVC and 4.5% for TDF/FTC. Category C events, grade 3/4 AEs and laboratory abnormalities were similar between the treatment arms. This study was prematurely stopped for inferior efficacy following a recommendation by the data monitoring committee.
Conclusions: At Week 48, MVC dosed once daily with DRV/r in a 2 drug-regimen showed inferior efficacy to TDF/FTC + DRV/r in antiretroviral-naïve subjects. The two CCR5-tropism assays (genotype or ESTA) were similar in predicting a positive treatment outcome. There were no new or unique safety findings.
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