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- Title
Broad Nucleoside-Analogue Resistance Implications for Human Immunodeficiency Virus Type 1 Reverse-Transcriptase Mutations at Codons 44 and 118.
- Authors
Romano, Laura; Venturi, Giulietta; Bloor, Stuart; Harrigan, Richard; Larder, Brendan A.; Major, Jennifer C.; Zazzi, Maurizio
- Abstract
Two large, independent human immunodeficiency virus type 1 resistance databases contain-ing .7700 reverse-transcriptase (RT) sequences were used to analyze the epidemiology of amino acid substitutions at codons 44 and 118, which confer moderate lamivudine resistance in the presence of zidovudine resistance. As expected, E44A/D and V118I mutations were strongly associated with M41L, D67N, L210W, and T215Y but also with other mutations, including K43E/N/Q, T69D, V75M, H208Y, R211K, and K219R. Both E44D and V118I were more frequently associated with stavudine and didanosine than with zidovudine and lamivudine treatment. How-ever, selection of E44A/D and V118I was also detected in association with a switch to other nu-cleoside RT inhibitors, including zalcitabine and abacavir. Site-directed mutagenesis confirmed that 44D and 118I can decrease phenotypic susceptibility not only to lamivudine but also to most other nucleoside analogues, particularly stavudine and abacavir. Thus, substitutions at RT co-dons 44 and 118 have broad implications in nucleoside RT inhibitor resistance in the setting of several nucleoside-associated mutations.
- Subjects
DRUG resistance; AIDS; PROTEASE inhibitors
- Publication
Journal of Infectious Diseases, 2002, Vol 185, Issue 7, p898
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/339706