How are drug-resistance mutations (DRMs) defined?
The association between a mutation and drug resistance is based on three types of correlations around which much of the database is organized: genotype-treatment correlations, genotype-phenotype correlations, and genotype-clinical outcome correlations. Genotype-treatment correlations indicate whether a mutation is selected by ARV drug therapy in vitro and/or in vivo. Genotype-phenotype correlations indicate whether a mutation reduces or contributes to reduced drug susceptibility in vitro. Genotype-phenotype correlations may be based on the susceptibility testing of laboratory isolates with site-directed mutants. More commonly, however, they are based on the susceptibility testing of clinical isolates containing multiple mutations. The association between mutations are reduced drug susceptibility will then often require statistical analyses because most drug-resistant isolates contain multiple DRMs (Rhee et al. 2006b). Genotype-clinical outcome correlations represent statistical associa
