TUAB0102 - Oral Abstract
Once-daily maraviroc in combination with ritonavir-boosted atazanavir in treatment-naïve patients infected with CCR5‑tropic HIV-1 (study A4001078): 96‑week results
Presented by Anthony Mills (United States).
A. Mills1, D. Mildvan2, D. Podzamczer3, G. Fätkenheuer4, M. Leal5, S. Than6, S.R. Valluri7, C. Craig8, M. Vourvahis7, J. Heera6, H. Valdez7, T. Brown9, A. Rinehart10, S. Portsmouth7
1Anthony Mills MD Inc., Los Angeles, United States, 2Beth Israel Medical Center Division of Infectious Diseases, New York, United States, 3HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain, 4First Department of Internal Medicine, University Hospital of Cologne, Köln, Germany, 5Infectious Disease Service, Virgen del Rocio University Hospital, Seville, Spain, 6Pfizer Inc., Groton, United States, 7Pfizer Inc., New York, United States, 8Pfizer Inc., Sandwich, United Kingdom, 9Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, United States, 10ViiV Healthcare, Research Triangle Park, United States
Background: Maraviroc (MVC) is a CCR5 antagonist approved for the treatment of CCR5‑tropic (R5) HIV‑1. This study evaluated a once-daily (QD), dual-therapy regimen of MVC plus atazanavir/ritonavir (ATV/r) in treatment-naïve patients; 96-week outcomes are presented.
Methods: In this Phase 2b, randomized, open-label study, 121 R5 HIV-1-infected patients received either MVC 150 mg QD (n=60) or tenofovir/emtricitabine (TDF/FTC) 200/300 mg QD (n=61) with ATV/r 300/100 mg QD for 48 weeks, later extended to 96 weeks. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL at Week 48.
Results: At Week 96, the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL was 67.8% (40/59) and 78.0% (46/59), respectively, for MVC versus 82.0% (50/61) and 83.6% (51/61), respectively, for TDF/FTC. Protocol-defined treatment failure occurred in 5 patients (MVC: n=3; TDF/FTC: n=2). Median change from baseline in CD4+ count was similar for both arms (MVC: 269 cells/mm3; TDF/FTC: 305 cells/mm3). Median change from baseline in creatinine clearance was -5.5 mL/min for MVC and -18 mL/min for TDF/FTC. Five patients (MVC: n=4; TDF/FTC: n=1) had plasma HIV-1 RNA >500 copies/mL at failure or study discontinuation; virologic analyses detected no resistance, change in tropism or loss of susceptibility relevant to treatment in either arm. At Week 48, there was a greater reduction in immune activation on CD4+ cells in patients receiving MVC versus TDF/FTC. Markers of bone formation were significantly different between arms at both 48 and 96 weeks.
Conclusions: Durable virologic activity of MVC 150 mg QD + ATV/r was demonstrated through 96 weeks, with no differences between the arms in the rates of virologic failure, no resistance or change in tropism seen, and with most of the treatment difference due to low-level transient viremia. Differences between the arms in immune activation and bone markers require further investigation.
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