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

✍ Scribed by Brigitte Montes; Michel Segondy

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 93 KB
• Volume: 66
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.2145

✦ Synopsis

Abstract

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 ≥ 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. J. Med. Virol. 66:299‐303, 2002. © 2002 Wiley‐Liss, Inc.