title: Darunavir inhibitory quotient predicts the 48-week virological response to darunavir-based salvage therapy in human immunodeficiency virus-infected protease inhibitor-experienced patients.
abstract: 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 (IC(50)) 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 IC(50) (P = 0.750). However, patients with darunavir vIQs of >or=1.5 had a 12-fold greater chance of achieving a >or=1 log(10) 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.
authors: Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Ctra de Canyet, Badalona, Barcelona, Spain. jmolto@flsida.org
authors: José
authors: J
authors: Moltó
authors: José R
authors: JR
authors: Santos
authors: Nuria
authors: N
authors: Pérez-Alvarez
authors: Samandhy
authors: S
authors: Cedeño
authors: Cristina
authors: C
authors: Miranda
authors: Saye
authors: S
authors: Khoo
authors: Laura
authors: L
authors: Else
authors: Josep Maria
authors: JM
authors: Llibre
authors: Marta
authors: M
authors: Valle
authors: Bonaventura
authors: B
authors: Clotet
mesh_terms: D000069454:Darunavir; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D016879:Salvage Therapy; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir