Abstract
Mutations that confer resistance to nucleoside analog reverse transcriptase inhibitors of HIV-1 can be divided into two major classes: thymidine analog mutations (TAMs) and TAM suppressors. M184V, K65R and L74V are TAM suppressors that emerge under the selective pressure of non-thymidine analogs. Each of the three TAM suppressors have been shown to decrease the level of resistance to 3´-azido-3´-deoxythymidine against a background of certain combinations of TAMs. L74V and M184V have also been associated with decreased phenotypic susceptibility to tenofovir disoproxil fumarate in vitro. In this review, the effects associated with the L74V mutation, which confer resistance to didanosine and abacavir, are discussed. The clinical significance of this mutation and the underlying biochemical mechanisms of inhibition, resistance and resensitization are also discussed in the context of drug regimens containing didanosine and/or abacavir, in combination with 3´-azido -3´-deoxythymidine and/or tenofovir disoproxil fumarate.
Published Version
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