title: Ability of different lopinavir genotypic inhibitory quotients to predict 48-week virological response in highly treatment-experienced HIV-infected patients receiving lopinavir/ritonavir.
abstract: The genotypic inhibitory quotient (GIQ) is the ratio between drug concentration and the number of resistance mutations. However, as different resistance scores can be calculated for the same protease inhibitor, the ability of a GIQ to predict the virological outcome may vary depending on the resistance score used as the denominator. Forty-four highly treatment-experienced HIV-infected patients failing on their current regimen were treated with a lopinavir/ritonavir-containing combination for at least 48 weeks. Three GIQs were calculated for each patient: the denominator of the first (GIQ-A) was the lopinavir/ritonavir score calculated using the mutations listed by IAS-USA as being related to lopinavir/ritonavir resistance; the denominator of the second (GIQ-B) was the total number of mutations related to resistance to any protease inhibitor as reported by IAS-USA; and the denominator of the third (GIQ-C) was the lopinavir/ritonavir score proposed by Parkin et al. The median (IQR) of the GIQ-A, B, and C was 4.69 (3.83-9.76), 0.97 (0.74-1.62), and 1.02 (0.68-2.52), respectively. At week 48, the median decrease in HIV-RNA was 1.09 (0.32-2.34) log(10) copies/ml (P < 0.0001), with 13 subjects (29.5%) attaining undetectable levels. All of the GIQs independently predicted the change in viral load from baseline and undetectable HIV-RNA at week 48. The partial R(2) of GIQ-C was greater than that of GIQ-B, which was greater than that of GIQ-A. All of the GIQs were independent predictors of the 48-week virological response. The predictive value of the GIQ for lopinavir/ritonavir may vary depending on the algorithm used to score drug resistance.
authors.affiliation: Clinic of Infectious Diseases, Università Vita-Salute San Raffaele, Milan, Italy. nicola.gianotti@hsr.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Anna
authors.initials: A
authors.lastname: Danise
authors.forename: Hamid
authors.initials: H
authors.lastname: Hasson
authors.forename: Enzo
authors.initials: E
authors.lastname: Boeri
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; 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 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D016333:HIV Protease; D019438:Ritonavir