Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients.
This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs.
Torti
Carlo
C
Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. torti.carlo@libero.it
Quiros-Roldan
Eugenia
E
Monno
Laura
L
Patroni
Andrea
A
Saracino
Annalisa
A
Angarano
Gioacchino
G
Tinelli
Carmine
C
Lo Caputo
Sergio
S
Tirelli
Valeria
V
Mazzotta
Francesco
F
Carosi
Giampiero
G
D019943:Amino Acid Substitution; D002219:Carbamates; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005663:Furans; D005814:Genes, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D061466:Lopinavir; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use; D012044:Regression Analysis; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D016333:HIV Protease