title: Prediction of virological response to lopinavir/ritonavir using the genotypic inhibitory quotient.
abstract: The predictive value of virological response to lopinavir (LPV)/ritonavir (r) was assessed in 126 HIV-infected patients who failed antiretroviral therapy and had begun a rescue intervention based on LPV/r. At 3 months, subjects with < or =6 protease (PRO) resistance mutations showed a higher rate of virological response (HIV-RNA drop > 1 log or to <50 copies/ml) than patients with >6 PRO resistance mutations (77% versus 48%; p = 0.01). On the other hand, virological responders had greater mean LPV plasma trough levels than nonresponders (6.4 versus 3.9 microg/ml; p = 0.02). A positive correlation was found between LPV trough concentration and viral load reductions at 3 months under LPV/r (r = 0.23; p = 0.017). Overall, virological response was seen in 80.8% of patients with LPV trough levels >4.8 microg/ml while in only 52.5% of patients with lower LPV trough concentrations (p = 0.002). In the multivariate analysis, both < or =6 PRO resistance mutations and LPV trough levels >4.8 microg/ml were independent predictors of virological response to salvage therapy with LPV/r. A genotypic inhibitory quotient (GIQ) was estimated for each patient based on the ratio between LPV trough levels and the number of PRO resistance mutations. A positive strong correlation was found between GIQ and viral load reductions (r = 0.42; p = 0.002). Virological response was seen in 78% of patients with a GIQ >0.7 but only in 41.6% of those with lower GIQ (p = 0.004). When LPV trough levels >4.8 microg/ml, PRO resistance mutations < or =6, and GIQ >0.7 were all included in a stepwise multivariate analysis, GIQ remained as the main independent predictor of response to LPV/r.
authors.affiliation: Pharmacology Unit, Hospital Carlos III, 28035 Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: González de Requena
authors.forename: Oscar
authors.initials: O
authors.lastname: Gallego
authors.forename: Luisa
authors.initials: L
authors.lastname: Valer
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jiménez-Nácher
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology; D016333:HIV Protease / Q000187:drug effects / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D009154:Mutation; D011237:Predictive Value of Tests; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000494:pharmacology; D016879:Salvage Therapy; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D016333:HIV Protease; D019438:Ritonavir