Abstract PE10/15
 
Lower Maraviroc Plasma Levels in Combination with Darunavir than with Other Protease Inhibitors Was Associated to Virological Failure - 24 Week Analysis of the MITOX Study Print
 
M.J. Obermeier1, H. Walter1, A. Wienbreyer1, S. Dupke1, A. Carganico1, I. Krznaric1, P. Ingiliz1, C. Cordes2, C. Mayr3, T. Wünsche4, C. Schuler5, S. Köppe6, R. Ehret1, B. Krüdewagen7, T. Berg1, A. Baumgarten1, MITOX Study Group
1Medizinisches Infektiologiezentrum Berlin, Berlin, Germany, 2Praxis Cordes, Berlin, Germany, 3MVZ Ärzteforum Seestrasse, Berlin, Germany, 4Praxis Wünsche, Berlin, Germany, 5Praxisgemeinschaft Turmstrasse, Berlin, Germany, 6Praxis Mehringdamm, Berlin, Germany, 7Deutsches Herzzentrum Berlin, Berlin, Germany
 
Objectives: The MITOX study was initiated to address toxicity and safety of switch strategies from NRTI-containing to NRTI-free and maraviroc (MVC) containing regimen. At week 24, only safety analyses were performed.
Methods: In this two-armed randomized prospective study 80 HIV-infected individuals with undetectable HIV plasma load receiving two NRTI+PI/r were randomized either to continue ART or to switch to MVC+PI/r regimen. Inclusion criteria were no contraindication to maraviroc, X4 tropism at screening from proviral DNA, and the absence of drug resistance to the current PI/r. Virological failure was defined as any viral load >50copies/ml at week 24.
Results: Forty patients in each arm were included. In week 24, six (MVC) and two patients (NRTI) were viremic with >50 copies/ml. Successful tropism testing during failure showed one switch to X4 tropism. No drug resistance was detected. Six patients returned to < 50 HIV-RNA copies/ml, four after a change of regimen, two without any change of ART. Four of six failing patients in the MVC arm received the combination of DRV/r+MVC, and three of those had insufficient MVC drug levels during failure. Analyses of all PI/r and MVC plasma exhibited lower mean (median) MVC levels of 234ng/ml (172ng/ml) when combined with DRV/r, and 410ng/ml (345ng/ml) combined with other PI/r (p=0.045). RTV plasma levels were significantly lower when combined with DRV, irrespective if combined with MVC (289 vs. 538ng/ml; p=0.028, see figure). PI/r plasma levels did not differ significantly.
[Ritonavir levels by DRV and MVC treatment]

Conclusion: In this study, failure at week 24 was caused frequently by insufficient MVC levels, but very rarely due to occurrence of X4 virus or drug resistance. The most frequently used combination, DRV/r+MVC, was associated with lower plasma levels of MVC and may have been caused by insufficient boosting due to lower RTV levels. DRV/r+MVC regimen should be monitored by therapeutic drug monitoring.


Assigned speakers:
Dr. med. Martin Obermeier , Medizinisches Infektiologiezentrum Berlin , Berlin , Germany

Assigned in sessions:
17.10.2013, 12:00-14:00, Poster Session, Poster Session 1, Exhibition
18.10.2013, 12:00-14:00, Poster Session, Poster Session 2, Exhibition