title: Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients.
abstract: Forty-nine protease inhibitor (PI)-experienced but amprenavir (APV)-naïve patients experiencing virological failure were treated with ritonavir (RTV) (100 mg twice a day [b.i.d.]) plus APV (600 mg b.i.d.). Patients responded to therapy with a median viral load decrease of -1.32 log(10) by week 12. The addition of low-dose RTV enhanced the minimal APV concentration in plasma (APV C(min)) up to 10-fold compared with that obtained with APV (1,200 mg b.i.d.) without RTV. Baseline PI resistance mutations (L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S, I84V) identified by univariate analysis and included in a genotypic score and APV C(min) at week 8 were predictive of the virological response at week 12. The response to APV plus RTV was significantly reduced in patients with six or more of the resistance mutations among the ones defined above. The genotypic inhibitory quotient, calculated as the ratio of the APV C(min) to the number of human immunodeficiency virus type 1 protease mutations, was a better predictor than the virological or pharmacological variables used alone. This genotypic inhibitory quotient could be used in therapeutic drug monitoring to define the concentrations in plasma needed to control replication of viruses with different levels of PI resistance, as measured by the number of PI resistance mutations.
authors.affiliation: Department of Virology, INSERM EMI 0214, Bichat-Claude Bernard Hospital, Paris, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Claire
authors.initials: C
authors.lastname: Lamotte
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Nadine
authors.initials: N
authors.lastname: Ktorza
authors.forename: Hocine
authors.initials: H
authors.lastname: Ait Mohand
authors.forename: Raquel
authors.initials: R
authors.lastname: Cacace
authors.forename: Manuela
authors.initials: M
authors.lastname: Bonmarchand
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Philippe
authors.initials: P
authors.lastname: Bossi
authors.forename: François
authors.initials: F
authors.lastname: Bricaire
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000328:Adult; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019438:Ritonavir