Document 0492
 DOCN  M9620492
 TI    Development of zidovudine resistance mutations in patients receiving
       prolonged didanosine monotherapy.
 DT    9602
 AU    Demeter LM; Nawaz T; Morse G; Dolin R; Dexter A; Gerondelis P; Reichman
       RC; Department of Medicine (Infectious Diseases Unit), University of;
       Rochester School of Medicine and Dentistry, New York 14642, USA.
 SO    J Infect Dis. 1995 Dec;172(6):1480-5. Unique Identifier : AIDSLINE
       MED/96083491
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Adult  Antiviral
       Agents/*THERAPEUTIC USE  Base Sequence  Didanosine/*THERAPEUTIC USE
       Drug Resistance/GENETICS  Female  Human  HIV-1/*DRUG EFFECTS  Male
       Molecular Sequence Data  *Mutation  RNA-Directed DNA
       Polymerase/*GENETICS  Support, U.S. Gov't, P.H.S.
       Zidovudine/*THERAPEUTIC USE  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).