Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 reverse transcriptase gene affect susceptibility to nucleoside analogs

The T69D mutation in the human immunodeficiency virus type 1 reverse transc riptase (RT) gene has been associated with reduced susceptibility to dideox ycytosine (ddC); however, several other mutations at codon 69 have been obs erved in antiretroviral drug-treated patients. The Stanford HIV RT and Prot ease Sequence Database was interrogated and showed that 23% of patients tre ated with nucleoside RT inhibitors (NRTI) had mutations at codon 69, These variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were pres ent 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-dd(l-containing regimens. Di fferent and specific patterns of other RT gene mutations were associated wi th the various codon 69 mutations, Drug susceptibility assays showed that v iral constructs containing codon 69 variants could have reduced susceptibil ity to ddC and other RT inhibitors, These results suggest that the T69D mut ation is not the only codon 69 variant associated with drug resistance and that ddC is not the only drug affected.