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

Abstract

Use of human immunodeficiency virus (HIV) drug-resistance testing in therapeutic decision making may be aided by understanding the relationship between results of genotypic and drug-susceptibility phenotypic assays. We investigated this relationship by applying 3 different statistical methods—cluster 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 extensive hard-gel SQV experience. Data include protease amino acid sequences and 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 partitioning is especially useful because it can identify interactions among mutations at different codons and accommodates many types of data as well as missing observations.