Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype

OBJECTIVES: To study the effect of the interruption of reverse transriptase inhibitor (RTI) therapy or a switch from RTI to protease inhibitors, on the genotypic drug-resistance pattern of plasma HIV-1. METHODS: Nine patients who completely stopped all medication, and five patients who switched from a treatment with RTI to a regimen containing protease inhibitors only, were studied. Direct sequencing of the plasma HIV-1 RT and protease gene was performed on follow-up samples taken before and after the interruption of treatment. RESULTS: Comparison of the amino acid sequence of the RT and protease genes in successive samples showed the rapid reappearance of wild-type viral variants in 12 of the 14 patients studied. Wild-type virus replaced the mutant strains 14 days to 2 months after the interruption of therapy, even in patients with a long treatment history. CONCLUSION: The results of this study indicate the sustained lower fitness of mutant strains in vivo. As a result, wild-type virus remains capable of outcompeting the RT or protease mutant strains very fast after removal of the drug. These findings highlight the importance of 'treatment history' in addition to genotypic and phenotypic markers determined at one time-point, when making therapeutic decisions for patients.