title: Prediction of early and confirmed virological response by genotypic inhibitory quotients for lopinavir in patients naïve for lopinavir with limited exposure to previous protease inhibitors.
abstract: OBJECTIVE
  To determine the impact of genotypic inhibitory quotient (GIQ) for lopinavir (LPV) in patients failing HAART with limited antiretroviral exposure.
  
  
  METHODS
  Retrospective analysis of a prospective trial.
  
  
  METHODS
  Lopinavir GIQ was calculated as the ratio between the mean trough concentration (C(trough)) and the number of protease mutations using eight different HIV drug resistance mutation lists or algorithms. Early (by week 12) and confirmed (up to week 24) virological response (HIV-RNA< 400 copies/mL, ECVR) was used as dependent variable in logistic regression model.
  
  
  RESULTS
  Seventy-one of 109 (65%) patients achieved ECVR. At multivariable logistic regression analysis, each mug/mL increase of GIQ was correlated with increasing probability of ECVR as far as the following mutations were computed: multi-protease inhibitor (PI) associated mutations listed by IAS (OR=1.17; 95% CI=0.99-1.39; P=0.058), mutations associated with LPV resistance by ANRS algorithm (OR=1.21; 95% CI=1.02-1.44; P=0.03), major mutations associated with LPV resistance by Stanford database (OR=1.16; 95% CI=1-1.35; P=0.05), and the whole set of mutations associated with LPV resistance in the same database (OR=1.22; 95% CI=1.02-1.46; P=0.03). Using ROC curve method, a specific threshold GIQ was assessed, above which this parameter could predict ECVR with the highest sensitivity (74.6% with GIQ obtained through Stanford LPV mutations) or specificity (89.5% with GIQ obtained through ANRS LPV mutations).
  
  
  CONCLUSIONS
  Our results suggest that increasing GIQ can improve virological outcome even in patients with limited exposure to PIs. Further studies are necessary to understand what HIV protease mutations should be considered and whether such mutations should be weighted differently to improve LPV GIQ predictive value.
authors.affiliation: Institute for Infectious and Tropical Diseases, University of Brescia, School of Medicine, Piazzale Spedali Civili 1, 25123 Brescia, Italy. torti.carlo@libero.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Uccelli
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: Franco
authors.initials: F
authors.lastname: Gargiulo
authors.forename: Valeria
authors.initials: V
authors.lastname: Tirelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Piera
authors.initials: P
authors.lastname: Pierotti
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Andrea
authors.initials: A
authors.lastname: Patroni
authors.forename: Nino
authors.initials: N
authors.lastname: Manca
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000187:drug effects / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D061466:Lopinavir; D008297:Male; D011237:Predictive Value of Tests; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D016333:HIV Protease