In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants.

摘要: Nevirapine-resistant variants were generated by serial passages in MT-2 cells the presence of increasing drug concentrations. In passage 5, mutations V106A, Y181C and G190A detected global population, associated with a 100-fold susceptibility decrease. Sequence analysis biological clones obtained from 5 subsequent showed that single mutants, first passages, progressively replaced 15 double correlating 500-fold increase phenotypic resistance. Fitness determination mutants confirmed that, nevirapine, every variant was more fit than wild-type fitness order Y181C>V106A>G190A>wild-type. Unexpectedly, absence drug, resistant mutant wild-type, gradient Y181C>wild-type >G106A⩾V190A. Using molecular clone which mutation introduced vitro mutagenesis, greater new competition cultures. These data exemplify role resistance on virus phenotype but also evolution leading, occasionally, to fitter drug.