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Antimicrobial Agents and Chemotherapy, May 2005, p. 1720-1726, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1720-1726.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Virological and Pharmacological Parameters Predicting the Response to Lopinavir-Ritonavir in Heavily Protease Inhibitor-Experienced Patients

Anne-Geneviève Marcelin,1* Isabelle Cohen-Codar,2 Martin S. King,3 Philippe Colson,4 Emmanuel Guillevic,2 Diane Descamps,5 Claire Lamotte,6 Véronique Schneider,7 Jacques Ritter,8 Michel Segondy,9 Hélène Peigue-Lafeuille,10 Laurence Morand-Joubert,11 Anne Schmuck,12 Annick Ruffault,13 Pierre Palmer,14 Marie-Laure Chaix,15 Vincent Mackiewicz,16 Véronique Brodard,17 Jacques Izopet,18 Jacqueline Cottalorda,19 Evelyne Kohli,20 Jean-Pierre Chauvin,2 Dale J. Kempf,3 Gilles Peytavin,6 and Vincent Calvez1

Department of Virology, Pitié-Salpêtrière, Paris,1 Department of Virology, La Timone, Marseille,4 Department of Virology, Bichat, Paris,5 Department of Virology, Tenon, Paris,7 Department of Virology, Lyon,8 Department of Virology, Montpellier,9 Department of Virology, Clermont-Ferrant,10 Department of Virology, Saint Antoine, Paris,11 Department of Virology, Grenoble,12 Department of Virology, Rennes,13 Department of Virology, Saint-Louis, Paris,14 Department of Virology, Necker, Paris,15 Department of Virology, Paul Brousse, Villejuif,16 Department of Virology, Reims,17 Department of Virology, Toulouse,18 Department of Virology, Nice,19 Department of Virology, Dijon, France,20 Abbott Laboratories, Rungis, France,2 Chicago, Ill.,3 Department of Pharmacy, Bichat Hospital, Paris, France6

Received 14 June 2004/ Returned for modification 23 August 2004/ Accepted 3 January 2005

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of –1.50 log10 copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state Cmin concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.

* Corresponding author. Mailing address: Department of Virology, Pitié-Salpêtrière Hospital, 83 Boulevard de l'hôpital, 75013 Paris, France. Phone: 33142177401. Fax: 33142177411. E-mail: anne-genevieve.marcelin{at}psl.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, May 2005, p. 1720-1726, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1720-1726.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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