title: Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients.
abstract: Amprenavir (APV) is an HIV protease inhibitor (PI) used for the treatment of either naive or PI-experienced HIV-infected patients. Several genotypic resistance pathways in protease gene have been described to be associated to unboosted APV failure (I50V, V32I + I47V, I54L/M, or less commonly I84V, which may be accompanied by one ore more accessory mutations such as L10F, L33F, M46I/L). The aims of this study were to investigate the efficacy up to week 24 of an APV plus ritonavir containing regimen in PI experienced patients and to determine the genotypic resistance profiles emerging in patients failing to this therapy. Forty-nine, PI experienced but APV naïve patients were treated with APV (600 mg bid) plus ritonavir (100 mg bid). By intent-to-treat analysis, the median decrease in viral load (VL) was -1.32 log10 (min +0.6; max -2.8) and -1.46 log10 (min +0.5; max -2.8) 12 and 24 weeks after initiating APV plus ritonavir regimen, respectively. Twelve patients harboured a VL >200 copies/ml at week 24. Among these patients, the selection of mutations previously described with the use of APV as first PI (V32I, L33F, M46I/L, I50V, 54M/L, and I84V) was observed. However, in some cases, mutations classically described after the use of other PIs (V82F and L90M) were selected but always with APV-specific mutations. There was no relation between the resistance pathways selected with either APV or ritonavir plasma minimal concentration, but higher APV plasma minimal concentration were associated with a lower rate of resistance mutations selection.
authors.affiliation: Department of Virology, Pitié-Salpêtrière Hospital, Paris, France. anne-genevieve.marcelin@psl.ap-hop-paris.fr
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Dissou
authors.initials: D
authors.lastname: Affolabi
authors.forename: Claire
authors.initials: C
authors.lastname: Lamotte
authors.forename: Hocine Ait
authors.initials: HA
authors.lastname: Mohand
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Delphine
authors.initials: D
authors.lastname: Voujon
authors.forename: Philippe
authors.initials: P
authors.lastname: Bossi
authors.forename: Nadine
authors.initials: N
authors.lastname: Ktorza
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; D019943:Amino Acid Substitution; D002219:Carbamates; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D006678:HIV / Q000187:drug effects* / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012641:Selection, Genetic; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease; D019438:Ritonavir