Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors.
It has been reported that a new pattern of mutations, E44D/A and/or V118I, in the reverse transcriptase (RT) gene of HIV-1 confers a moderate level of resistance to lamivudine in the absence of the M184V mutation. The prevalence of this mutational pattern was studied in HIV-1 isolates obtained from 280 patients. These mutations were not identified in the RT sequences from 23 antiretroviral-naive patients but were detected in 82 (31.9%) of the 257 RT sequences obtained from nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients. Mutation at codon 44 was identified in 41 patients (7 mutations E44A and 34 mutations E44D), mutation V118I was identified in 73 patients and a combination of mutations at codons 44 and 118 was found in 32 patients. Multivariate analysis showed an association between the E44D/A and/or V118I mutational pattern and the RT mutations D67N, T69D, L210W, and T215Y/F. No relationship was observed between this mutational pattern and the lamivudine-specific resistance mutation M184V. The prevalence of these mutations increased significantly with the number of drug regimens experienced and a prevalence of 42.4% was observed in patients who had received >or= 4 antiretroviral regimens. A relationship was found between the E44D/A and/or V118I mutational pattern and experience with didanosine or stavudine but not with lamivudine. The results suggest that the development of the E44D/A and/or V118I mutational pattern is frequent in patients treated with NRTIs. Thymidine analogues and didanosine, but not lamivudine, could promote the development of these mutations.
Montes
Brigitte
B
Laboratoire de Virologie, Centre Hospitalier et Universitaire (CHU), Montpellier, France.
Segondy
Michel
M
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003853:Deoxyribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D016296:Mutagenesis; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D003853:Deoxyribonucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase