Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS Clinical Trials Group protocol 333

AIDS Clinical Trials Group protocol 333 was an open-label trial of a switch from saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinav ir soft-gel capsules (SQVsgc) after >48 weeks of prior treatment with SQVhc , Eighty-nine subjects received IDV or SQVsgc or continued to receive SQVhc and continued unchanged treatment with non-protease-inhibitor antivirals f or 8 weeks. Subjects receiving SQVhc then switched treatment to IDV. Baseli ne drug susceptibility and protease gene sequencing were done; 12 codons re lated to IDV and SQV resistance were analyzed. After 112 weeks (median) of SQVhc, the fall in human immunodeficiency virus (HIV) type 1 RNA level from baseline was significantly greater with IDV and was inversely correlated w ith the number of protease substitutions. The number of substitutions also correlated with baseline CD4 cell count, HIV-1 RNA level, SQV experience, a nd drug susceptibility. Substitution at codon 10, which occurred only in is olates with greater than or equal to 2 substitutions, was associated with b lunted RNA response. IDV IC50 correlated with HIV-1 RNA response after the switch to IDV but added little predictive power once the genotype was consi dered.