title: Genotypic resistance to lopinavir and fosamprenavir with or without ritonavir of clinical isolates from patients failing protease inhibitors-containing HAART regimens: prevalence and predictors.
abstract: The aim of this study was to establish the prevalence and predictors of genotypic resistance of HIV-1 to lopinavir and fosamprenavir from patients failing protease inhibitors (PI)-based regimens. We selected 643 HIV-1-infected patients with available treatment history who underwent genotypic resistance assays for virological failure from a clinical site and from the Stanford database. According to the genotypic resistance interpretation of the Stanford algorithm, proportions of viruses showing full susceptibility to fosamprenavir and lopinavir were 32% and 34%, respectively (p =ns). Proportions of viruses fully susceptible to lopinavir/r and fosamprenavir/r according to the Agence Nationale pour la Recherche sur le SIDA (ANRS) algorithm, were 81% and 81%, respectively. According to the Rega algorithm, proportions of viruses showing full susceptibility to fosamprenavir/r and lopinavir were 80% and 70%, respectively (p<0.001). According to the ANRS and Rega interpretations, the time on therapy predicted susceptibility to lopinavir/r, while susceptibility to fosamprenavir/r according to ANRS was predicted by the number of prior PI regimens experienced. According to the Stanford interpretation, prior indinavir exposure predicted resistance to lopinavir/r and fosamprenavir/r while prior nelfinavir use predicted susceptibility to both drugs. After failing PI-based regimens, the majority of viruses retained a predicted susceptibility to fosamprenavir/r and lopinavir/r. In patients failing PIs, the interpretation of genotypic resistance to fosamprenavir may change considerably according to the different algorithms and in respect to the effect of pharmacokinetic boosting with ritonavir.
authors: Institute of Clinical Infectious DiseasesCatholic University, Rome, Italy. simona.digiambenetto@rm.unicatt.it
authors: Simona
authors: S
authors: Di Giambenedetto
authors: Alessanra
authors: A
authors: Bacarelli
authors: Carmen
authors: C
authors: Pinnetti
authors: Manuela
authors: M
authors: Colafigli
authors: Mattia
authors: M
authors: Prosperi
authors: Giorgio
authors: G
authors: Gatti
authors: Roberto
authors: R
authors: Cauda
authors: Andrea
authors: A
authors: De Luca
mesh_terms: D000328:Adult; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D002219:Carbamates / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D005663:Furans; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D061466:Lopinavir; D008297:Male; D010755:Organophosphates / Q000627:therapeutic use; D015995:Prevalence; D011744:Pyrimidinones / Q000627:therapeutic use; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; C426859:fosamprenavir