Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy.
Human immunodeficiency virus type 1 (HIV-1) isolates from 2 patients who received didanosine (ddI) monotherapy for > 2 years were analyzed for reverse transcriptase (RT) mutations by sequencing of proviral DNA from peripheral blood mononuclear cell cultures. One patient was otherwise antiretroviral-naive; the other had received zidovudine for 5 months before beginning ddI therapy. Isolates obtained from both patients before initiation of ddI monotherapy were free of HIV-1 RT mutations associated with zidovudine or ddI resistance. However, after prolonged ddI monotherapy, mutations associated with zidovudine resistance (M41L, D67N, K70R, and/or T215Y) were detected in HIV-1 isolates from both patients. There was no evidence that surreptitious use of zidovudine or technical artifact caused these findings. This observation suggests that prolonged ddI monotherapy may decrease the efficacy of subsequent zidovudine therapy in some patients.
Demeter
L M
LM
Department of Medicine (Infectious Diseases Unit), University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Nawaz
T
T
Morse
G
G
Dolin
R
R
Dexter
A
A
Gerondelis
P
P
Reichman
R C
RC
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D016049:Didanosine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine