Département de virologie et immunologie biologique, CHU de Bordeaux
We describe in this review the molecular mechanisms of HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTI). Resistance mutations in the RT gene have been characterized for each drug within this class; they can mediate resistance through two mechanisms: i) Some mutations (M184V, Q151M) induce a discrimination in favour of the natural nucleotide compared to the NRTI triphosphate, leading to resistance by decreasing the incorporation of the inhibitor; ii) other changes, including TAMs (Thymidine analog mutations) act through an increase of NRTI-MP-excision after the incorporation of the NRTI during DNA chain synthesis. We also describe a mixed resistance mechanism for the K65R mutation, and interactions between mutations leading to HIV resensitization to some drugs. Finally, we describe the different strategies designed to fight against resistance to NRTI.