Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients.
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.
Marcelin
Anne-Geneviève
AG
Department of Virology, Pitié-Salpêtrière Hospital, Paris, France. anne-genevieve.marcelin@psl.ap-hop-paris.fr
Affolabi
Dissou
D
Lamotte
Claire
C
Mohand
Hocine Ait
HA
Delaugerre
Constance
C
Wirden
Marc
M
Voujon
Delphine
D
Bossi
Philippe
P
Ktorza
Nadine
N
Bricaire
François
F
Costagliola
Dominique
D
Katlama
Christine
C
Peytavin
Gilles
G
Calvez
Vincent
V
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
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease; D019438:Ritonavir