HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine.
Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-level resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), develops rarely during therapy with NNRTIs plus zidovudine. To determine whether didanosine (ddI) is also effective in preventing the emergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and reverse transcriptase sequences of isolates obtained from patients enrolled in a pharmacokinetic study of DLV and ddI. Nine NNRTI-naive patients were evaluated. Seven received DLV/ddI and two received DLV/ddI/zidovudine. Median durations of prior zidovudine and ddI were 26 and 15 months, respectively. Isolates from eight of nine patients had a mutation(s) associated with nucleoside resistance at entry. After treatment with DLV and ddI alone, isolates from five of seven patients developed Y181C, four in combination with K103N. Thus, in this group of nucleoside-experienced patients, combination therapy with DLV/ddI did not prevent the emergence of Y181C.
Demeter
L M
LM
Infectious Diseases Unit, University of Rochester, New York 14642, USA.
Meehan
P M
PM
Morse
G
G
Gerondelis
P
P
Dexter
A
A
Berrios
L
L
Cox
S
S
Freimuth
W
W
Reichman
R C
RC
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020008:Delavirdine; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D010641:Phenotype; D010879:Piperazines / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D007211:Indoles; D010879:Piperazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D020008:Delavirdine; D054303:HIV Reverse Transcriptase; D016049:Didanosine