HIV-1 DRUG SUSCEPTIBILITIES AND REVERSE-TRANSCRIPTASE MUTATIONS IN PATIENTS RECEIVING COMBINATION THERAPY WITH DIDANOSINE AND DELAVIRIDINE

Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-le vel resistance to nonnucleoside reverse transcriptase inhibitors (NNRT Is), develops rarely during therapy with NNRTIs plus zidovudine. To de termine whether didanosine (ddI) is also effective in preventing the e mergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and r everse transcriptase sequences of isolates obtained from patients enro lled in a pharmacokinetic study of DLV and ddI. Nine NNRTI-naive patie nts were evaluated. Seven received DLV/ddI and two received DLV/ddI/zi dovudine. Median durations of prior zidovudine and ddI were 26 and 15 months, respectively. Isolates from eight of nine patients had a mutat ion(s) associated with nucleoside resistance at entry. After treatment with DLV and ddI alone, isolates from five of seven patients develope d Y181C, four in combination with K103N. Thus, in this group of nucleo side-experienced patients, combination therapy with DLV/ddI did not pr event the emergence of Y181C.