TUPE099 - Poster Exhibition
Week 48 results of the Maraviroc Plus Darunavir/ritonavir Study (MIDAS) for treatment-naive patients infected with R5-tropic HIV-1
B. Taiwo1, S. Swindells2, B. Berzins1, E. Acosta3, P. Ryscavage1, J. Lalezari4, J. Castro5, O. Adeyemi6, B. Yip1, M. Rathert1, D. Kuritzkes7, J. Eron8, MIDAS Study Team
1Northwestern University, Division of Infectious Diseases, Chicago, United States, 2University of Nebraska, Omaha, United States, 3University of Alabama, Birmingham, United States, 4Quest Clinical Research, San Francisco, United States, 5University of Miami, Miami, United States, 6CORE Center, Chicago, United States, 7Harvard University, Cambridge, United States, 8University of North Carolina at Chapel Hill, Chapel Hill, United States
Background: Novel NRTI-sparing regimens are needed to address transmitted NRTI resistance or toxicity.
Methods: Treatment-naïve HIV-1-infected patients received maraviroc (MVC) 150 mg plus darunavir/ritonavir (DRV/r) 800/100 mg once-daily. Inclusion required viral load (VL) 5,000 to 500,000 c/ml, R5 tropism on enhanced sensitivity Trofile assay and CD4 > 100 cells/mm3. Patients with any DRV resistance mutation were excluded. Primary endpoint was virologic failure (VF) = confirmed VL > 50 c/ml at wk 24 or later, using intent-to-treat analysis (missing/off study without VF ignored). Adherence was perfect (no missed doses) or imperfect. MVC Ctrough was determined at wks 2,4,12 and 24.
Results: Twenty-five subjects enrolled; median age 38 yrs, 88% male, 60% white. Baseline median CD4 and VL were 455 cell/mm3 and 42,050 c/ml. One subject never initiated treatment. VF occurred in 3/24 subjects (12.5 % [95% CI 2.7, 32.4]) at wk 24. By wk 48, VF occurred in 4/24 subjects (16.7% [4.7, 37.4]). Of the 4 patients with baseline VL > 100,000 c/ml, 3 (75%) experienced VF: 2 never suppressed (VL at VF = 82 c/ml and 224 c/ml); and 1 suppressed to < 50 c/ml then rebounded at wk 36 (VL at VF 94 c/ml). 1/20 (5%) subjects with baseline VL < 100,000 c/ml had VF (rebounded to 989 c/ml at wk 24). Baseline VL >100,000 c/ml was associated with VF (p = 0.008, Fisher's exact test). All VF subjects reported perfect adherence. Geometric-mean MVC Ctrough was 24 to 39 ng/mL, similar in VFs and non-VFs. Both rebounders resuppressed without changing treatment. Median CD4 increased 247 cells/mm3 by wk 48. LDL-cholesterol increased to grade 3 in one patient.
Conclusions: MVC/DRV/r 150/800/100 mg once-daily was well-tolerated and effective, but VF occurred in 3/4 patients with baseline VL > 100,000 c/ml. These findings should be evaluated with caution in larger randomized studies.
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