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 antiretrovira...

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Bibliographic Details
Published in:The Journal of infectious diseases 1995-12, Vol.172 (6), p.1480-1485
Main Authors: Demeter, Lisa M., Nawaz, Taimor, Morse, Gene, Dolin, Raphael, Dexter, Angela, Gerondelis, Peter, Reichman, Richard C.
Format: Article
Language:English
Subjects:
Acquired Immunodeficiency Syndrome - drug therapy
Adult
AIDS/HIV
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiretrovirals
Antiviral agents
Antiviral Agents - therapeutic use
Base Sequence
Biological and medical sciences
Codons
Didanosine - therapeutic use
DNA
Drug Resistance - genetics
Female
Genetic mutation
HIV
HIV 1
HIV Reverse Transcriptase
HIV-1 - drug effects
human immunodeficiency virus 1
Humans
Infections
Major Articles
Male
Medical sciences
Molecular Sequence Data
Mutation
Pharmacology. Drug treatments
Polymerase chain reaction
RNA-Directed DNA Polymerase - genetics
Sequencing
Viruses
Zidovudine - therapeutic use
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/172.6.1480