Methods for investigation of the relationship between drug-susceptibility phenotype and human immunodeficiency virus type 1 genotype with applications to AIDS Clinical Trials Group 333

Use of human immunodeficiency virus (HIV) drug-resistance testing in therap eutic decision making may be aided by understanding the relationship betwee n results of genotypic and drug-susceptibility phenotypic assays. We invest igated this relationship by applying 3 different statistical methods - clus ter analysis, recursive partitioning, and linear discriminant analysis - to results for 72 patients followed in the Adult AIDS Clinical Trials Group ( ACTG) protocol 333, ACTG 333 was a multicenter, randomized trial comparing 2 formulations of saquinavir (SQV) to indinavir (IDV) in patients with exte nsive hard-gel SQV experience. Data include protease amino acid sequences a nd 50% inhibitory concentrations for SQV and IDV at baseline, The 3 methods give similar results showing the association of mutations at codons 10, 63 , 71, and 90 with in vitro resistance to IDV and SQV, Recursive partitionin g is especially useful because it can identify interactions among mutations at different codons and accommodates many types of data as well as missing observations.