Mechanisms of Resistance to Nucleosides Unraveled

Until recently, the selection of distinct, specificmutations at the RT gene was supposed toaccount for the emergence of resistance to eachof the different nucleoside analogues. Forinstance, 184V resulted in a loss of sensitivity to3TC, 74V to ddI, and 215Y to AZT. However, themutations accounting for the lack of sensitivity tod4T remained unknown and mysterious, since75T was only rarely detected in vivo. Morerecently, it was shown that multi-nucleoside resistantgenotypes (151M complex and 69 inserts)represented an additional pathway leading tod4T resistance. But again, these genotypes areselected in less than 5% of subjects failing anyd4T-containing combination.