
<ArticleTitle>Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 <prot>reverse transcriptase</prot> gene affect susceptibility to nuleoside analogs.</ArticleTitle>
<AbstractText>The T69D mutation in the human immunodeficiency virus type 1 <prot>reverse transcriptase</prot> (<prot>RT</prot>) gene has been associated with reduced susceptibility to dideoxycytosine (ddC); however, several other mutations at codon 69 have been observed in antiretroviral drug-treated patients. The Stanford HIV <prot>RT</prot> and Protease Sequence Database was interrogated and showed that 23% of patients treated with nucleoside <prot>RT</prot> inhibitors (NRTI) had mutations at codon 69. These variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were present in patients treated with NRTI but not in drug-naive patients. Treatment history information showed that a substantial percentage of these codon 69 changes occurred in patients administered non-ddC-containing regimens. Different and specific patterns of other <prot>RT</prot> gene mutations were associated with the various codon 69 mutations. Drug susceptibility assays showed that viral constructs containing codon 69 variants could have reduced susceptibility to ddC and other <prot>RT</prot> inhibitors. These results suggest that the T69D mutation is not the only codon 69 variant associated with drug resistance and that ddC is not the only drug affected.</AbstractText>
