Comparison of protease genotype and phenotype in HIV-1 infected patients exposed to more than one protease inhibitor.
Many patterns of mutations selected by HIV-1 protease inhibitors have been described, but in most cases isolates with these patterns have been obtained from pre-clinical studies or after failures of monotherapies. We compared genotype and phenotype in HIV-1 infected patients who have failed more than one PI-including regimen. Phenotypic resistance could arise also in the absence of specific primary mutations and in the presence of different substitutions among those known to confer resistance to ritonavir, indinavir or nelfinavir. The number of secondary mutations was significantly associated with phenotypic resistance for each protease inhibitor. Thus, more study of mutational patterns in heavily pretreated patients is warranted; in the mean time treatment choices might be optimized if phenotyping could integrate genotyping within this setting.
Gianotti
N
N
Division of Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. gianotti.nicola@hsr.it
Tambussi
G
G
Boeri
E
E
Lazzarin
A
A
D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype
D017320:HIV Protease Inhibitors; D016333:HIV Protease