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Antimicrobial Agents and Chemotherapy, November 2008, p. 3928-3932, Vol. 52, No. 11
0066-4804/08/$08.00+0 doi:10.1128/AAC.00520-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Darunavir Inhibitory Quotient Predicts the 48-Week Virological Response to Darunavir-Based Salvage Therapy in Human Immunodeficiency Virus-Infected Protease Inhibitor-Experienced Patients
José Moltó,1*
José R. Santos,1
Nuria Pérez-Álvarez,1,2
Samandhy Cedeño,3
Cristina Miranda,1
Saye Khoo,4
Laura Else,4
Josep Maria Llibre,1
Marta Valle,5 and
Bonaventura Clotet1,3
Lluita contra la SIDA Foundation,1 IrsiCaixa Foundation, Hospital Universitari Germans Trias i Pujol, Badalona,3 Universitat Politécnica de Barcelona,2 Centre d'Investigació del Medicament, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Spain,5 Pharmacology Department, University of Liverpool, Liverpool, United Kingdom4
Received 22 April 2008/ Returned for modification 18 July 2008/ Accepted 15 August 2008
The aim of this study was to evaluate the relationship between the virological response to darunavir-based salvage antiretroviral therapy and the darunavir genotypic and virtual inhibitory quotients (gIQ and vIQ, respectively). Thirty-seven HIV-infected patients failing protease inhibitor-based antiretroviral regimens who started salvage therapy containing darunavir-ritonavir were prospectively studied. The primary outcome of the study was a viral load (VL) of <50 copies/ml at week 48. The trough concentrations of darunavir in plasma, the number of darunavir resistance mutations, the change in the 50% inhibitory concentration (IC50) of darunavir in the virtual phenotype, and the darunavir gIQ and vIQ were correlated with the virological outcome in regression analyses adjusted by the number of active drugs in the background regimen. The VL was <50 copies/ml in 56.8% of patients at week 48. Changes in the VL were not significantly associated with the darunavir concentration (P = 0.304), the number of darunavir resistance mutations (P = 0.695), or the change in the IC50 (P = 0.750). However, patients with darunavir vIQs of 
1.5 had a 12-fold greater chance of achieving a 1 log10 reduction in the VL (odds ratio [OR], 12.7; 95% confidence interval [95% CI], 1.9 to 81.6; P = 0.007), and a 5-fold greater chance of achieving a VL of <50 copies/ml (OR, 5.4; 95% CI, 1.2 to 24.5; P = 0.028), at week 48 than patients with darunavir vIQs of <1.5. The positive and negative predictive values of this darunavir vIQ cutoff for achieving a VL of <50 copies/ml at week 48 were 70% and 69%, respectively. The darunavir vIQ predicts virological response to darunavir-based salvage therapy better than the darunavir trough concentration or resistance mutations alone. We suggest targeting a darunavir vIQ of 1.5 for achieving long-term viral suppression.
* Corresponding author. Mailing address: Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Ctra de Canyet, s/n. 08916 Badalona, Barcelona, Spain. Phone: 34 93 497 88 87. Fax: 34 93 465 76 02. E-mail: jmolto{at}flsida.org
Published ahead of print on 25 August 2008.
Antimicrobial Agents and Chemotherapy, November 2008, p. 3928-3932, Vol. 52, No. 11
0066-4804/08/$08.00+0 doi:10.1128/AAC.00520-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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