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Antimicrobial Agents and Chemotherapy, November 2008, p. 4050-4056, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00605-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Virologic Response to Lopinavir-Ritonavir-Based Antiretroviral Regimens in a Multicenter International Clinical Cohort: Comparison of Genotypic Interpretation Scores{triangledown}

Philip Grant,1* Eric C. Wong,1 Richard Rode,2 Robert Shafer,1 Andrea De Luca,3 Jeffrey Nadler,4 Trevor Hawkins,5 Calvin Cohen,6 Robert Harrington,7 Dale Kempf,2 and Andrew Zolopa1

Stanford University, Palo Alto, California,1 Abbott Laboratories, Abbott Park, Illinois,2 Università Cattolica del Sacro Cuore, Rome, Italy,3 University of South Florida, Tampa, Florida,4 University of New Mexico, Santa Fe, New Mexico,5 Community Research Initiative of New England, Boston, Massachusetts,6 University of Washington, Seattle, Washington7

Received 8 May 2008/ Returned for modification 16 June 2008/ Accepted 7 August 2008

Several genotypic interpretation scores have been proposed for the evaluation of susceptibility to lopinavir/ritonavir (LPV/r) but have not been compared using an independent data set. This study was a retrospective multicenter cohort of patients initiating LPV/r-based therapy. The virologic response (VR) was defined as a viral load of <500 copies/ml at week 24. The genotypic interpretation scores surveyed were the LPV mutation score, the ViroLogic score, the ATU score, the Stanford database score, and the International AIDS Society-USA mutation list. Of the 103 patients included in the analysis, 76% achieved VR at 24 weeks. For scores with clinical breakpoints defined (LPV mutation, ATU, ViroLogic, and Stanford), over 80% of the patients below the breakpoints achieved VR, while 50% or less above the breakpoints responded. Protease mutations at positions 10, 54, and 82 and at positions 54, 84, and 90 were associated with a lack of VR in the univariate and multivariate analyses, respectively. The area under the receiver-operator characteristic curves for the five genotypic interpretation scores studied ranged from 0.73 to 0.76. The study confirms that the currently available genotypic interpretation scores which are widely used by clinicians performed similarly well and can be effectively used to predict the virologic activity of LPV/r in treatment-experienced patients.

* Corresponding author. Mailing address: Division of Infectious Diseases and Geographic Medicine, 300 Pasteur Drive, Grant Building Room S-169, Stanford, CA 94305-5107. Phone: (650) 354-8107. Fax: (650) 354-8102. E-mail: pmgrant{at}stanford.edu

{triangledown} Published ahead of print on 18 August 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 4050-4056, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00605-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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