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 obtaine d from pre-clinical studies or after failures of monotherapies. We compared genotype and phenotype in HIV-1 infected patients who have failed more tha n one PI-including regimen. Phenotypic resistance could arise also in the a bsence of specific primary mutations and in the presence of different subst itutions 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 me an time treatment choices might be optimized if phenotyping could integrate genotyping within this setting.