Darunavir Inhibitory Quotient predicts the 48-week virological response to Darunavir-Based Salvage Theraphy in HIV-Infected Protease Inhibitor-Experienced Patients.

Darunavir Inhibitory Quotient predicts the 48-week virological response to Darunavir-Based Salvage Theraphy in HIV-Infected Protease Inhibitor-Experienced Patients.

Online publication: 25/08/2008

Abstract:

The aim of this study was to evaluate the relationship between virological response to darunavir-based salvage antiretroviral therapy and the darunavir genotypic and virtual inhibitory quotient (gIQ, vIQ). 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 viral load (VL) <50 copies/mL at week 48. Darunavir trough plasma concentrations, the number of darunavir resistance mutations, the fold change in darunavir IC50 in the virtual phenotype, and darunavir gIQ and vIQ were correlated with the virological outcome in regression analyses adjusted by the number of active drugs in the background regimen. VL was <50 copies/mL in 56.8%patients at week 48. Changes in VL were not significantly associated with darunavir concentration (P = 0.304), the number of darunavir resistance mutations (P = 0.695), or fold change in IC50 (P = 0.750) respectively. However, patients with a darunavir vIQ >/=1.5 had a 12-fold greater chance of achieving a >/=1 log10 reduction in VL (OR 12.7; 95% CI, 1.9-81.6; P = 0.007), and a 5-fold greater chance of achieving a VL <50 copies/mL (OR 5.4; 95% CI, 1.2-24.5; P = 0.028) at week 48, compared with patients with a darunavir vIQ <1.5. The positive and negative predictive values of this darunavir vIQ cut-off for achieving VL <50 copies/mL at week 48 were 70% and 69%, respectively. Darunavir vIQ predicts virological response to darunavir-based salvage therapy better than darunavir trough concentration or resistance mutations alone. We suggest targeting a darunavir vIQ of 1.5 for achieving long-term viral suppression.

Authors: Moltó J, Santos JR, Pérez-Álvarez N, Cedeño S, Miranda C, Khoo S, Else L, Llibre JM, Valle M, Clotet B.
  • Doi Code: Antimicrob Agents Chemother. 2008 Aug 25. [Epub ahead of print]

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