Genotypic resistance to lopinavir and fosamprenavir with or without ritonavir of clinical isolates from patients failing protease inhibitors-containing HAART regimens: prevalence and predictors.
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.
Di Giambenedetto
Simona
S
Institute of Clinical Infectious DiseasesCatholic University, Rome, Italy. simona.digiambenetto@rm.unicatt.it
Bacarelli
Alessanra
A
Pinnetti
Carmen
C
Colafigli
Manuela
M
Prosperi
Mattia
M
Gatti
Giorgio
G
Cauda
Roberto
R
De Luca
Andrea
A
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
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; C426859:fosamprenavir