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Antimicrobial Agents and Chemotherapy, July 2009, p. 2934-2939, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01643-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protease Inhibitor Resistance Analysis in the MONARK Trial Comparing First-Line Lopinavir-Ritonavir Monotherapy to Lopinavir-Ritonavir plus Zidovudine and Lamivudine Triple Therapy{triangledown}

Constance Delaugerre,1* Philippe Flandre,2 Marie Laure Chaix,1 Jade Ghosn,1,3 François Raffi,4 Pierre Dellamonica,5 H. Jaeger,6 D. Shürmann,7 Isabelle Cohen-Codar,8 Philippe Ngo Van,8 Michael Norton,9 Anne-Marie Taburet,10 Jean-François Delfraissy,3 Christine Rouzioux,1 for the MONARK Study Group

University Paris Descartes, EA 3620, Virology Department, Necker Hospital AP-HP, Paris, France,1 INSERM U 720, Pierre and Marie Curie University, Paris, France,2 Department of Internal Medicine and Infectious Diseases, Bicêtre University Hospital AP-HP, Le Kremlin-Bicêtre, France,3 Infectious Diseases, University Hospital, Nantes, France,4 Infectious Diseases, University Hospital, Nice, France,5 MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, Germany,6 Infectious Diseases, Berlin, Germany,7 Abbott Laboratories, Rungis, France,8 Abbott Laboratories, Whippany, New Jersey,9 Laboratory of Clinical Pharmacology, Bicêtre University Hospital AP-HP, Le Kremlin-Bicêtre, France,10

Received 15 December 2008/ Returned for modification 3 March 2009/ Accepted 8 May 2009

The MONARK study was a pilot randomized trial comparing the safety and efficacy of lopinavir-ritonavir (LPV/r) monotherapy to those of LPV/r-zidovudine-lamivudine triple therapy for antiretroviral-naïve human immunodeficiency virus type 1 (HIV-1)-infected patients. Resistance testing was performed at the time of initial screening and at the time of virological failure (defined to include low-level viremia with >50 and <400 HIV-1 virus RNA copies/ml of plasma). Changes from the baseline sequences, including mutations noted on the 2008 International AIDS Society—USA list of resistance-associated protease mutations, were considered. Drug resistance testing was performed for 38 patients (5 of 53 on triple therapy and 33 of 83 on monotherapy). By week 96 (W96), virus samples from 18 of 33 patients in the monotherapy arm showed changes from baseline sequences, and 5 of these patients had viruses with major protease inhibitor (PI) resistance-associated mutations (M46I at W40, L76V at W48, M46I and L76V at W48, L10F and V82A at W72, and L76V at W84). Data on virus phenotypes detected at the time of initial screening and the time of virological failure were available for four patients in whom major PI resistance mutations developed, and these data revealed a mean increase of 2.2-fold (range, 0.75- to 4.6-fold) in the LPV 50% inhibitory concentration. All three patients in whom the L76V PI resistance mutation developed were infected with HIV-1 subtype CRF02_AG. In the triple-therapy group, no major PI resistance mutation was selected among the three patients with protease changes by W48. No association between the baseline CD4 cell count and the viral load, the W4 and final viral loads, or the final LPV trough concentration and the emergence of a major PI resistance mutation was found. Major PI resistance-associated mutations were detected in 5 (6%) of 83 patients treated with LPV/r monotherapy, suggesting that LPV/r monotherapy is an inappropriate first option. The mutation L76V may be considered in further studies of lopinavir resistance.

* Corresponding author. Mailing address: Virology Department, Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010 Paris, France. Phone: 33 1 42 49 94 90. Fax: 33 1 42 49 92 00. E-mail: constance.delaugerre{at}sls.aphp.fr

{triangledown} Published ahead of print on 18 May 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2934-2939, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01643-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • (2009). Failure on First-Line Lopinavir/r Monotherapy: High Rates of PI Resistance. AIDS Clin Care 2009: 2-2 [Full Text]  


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