Document 0343
 DOCN  M94A0343
 TI    HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in
       children treated with zidovudine.
 DT    9412
 AU    Principi N; Marchisio P; De Pasquale MP; Massironi E; Tornaghi R; Vago
       T; Pediatric Department (IV), University of Milan, Italy.
 SO    AIDS Res Hum Retroviruses. 1994 Jun;10(6):721-6. Unique Identifier :
       AIDSLINE MED/94355118
 AB    OBJECTIVE: In HIV-infected adults prolonged monotherapy with zidovudine
       may be associated with the appearance of HIV strains with decreased
       zidovudine sensitivity, owing to specific mutations in the reverse
       transcriptase (RT) gene, and this has been suggested to be a reason for
       reduced zidovudine efficacy. This study was undertaken to determine the
       appearance of mutation at codon 215 of the RT gene in proviral DNA from
       PBMCs in HIV-infected children. DESIGN: A prospective, open study.
       SETTING: A University Pediatric Department. PATIENTS AND METHODS:
       Nineteen HIV-infected symptomatic children were treated with zidovudine
       for a median of 24 months. Clinical and laboratory controls for HIV
       infection status were performed monthly. Mutant proviral sequences were
       evaluated at the start of therapy, every 3 months during the first 6
       months of therapy, and every 6 months thereafter. Clinical outcome was
       defined as stable or deteriorating. RESULTS: No child had proviral
       sequences mutant at codon 215 before starting zidovudine. Ten of 13
       children who had received zidovudine for more than 6 months developed
       mutant proviral sequences. All the children (10 of 10) with mutant
       proviral sequences had a deteriorating clinical condition, compared to
       none of those (0 of 9) without mutation at codon 215. CONCLUSION: The
       appearance of HIV-1 codon 215 mutation seems to be strongly associated
       with zidovudine therapy and with clinical progression of HIV disease in
       children.
 DE    Base Sequence  Child  Child, Preschool  Drug Resistance, Microbial  DNA
       Probes  Human  HIV Infections/*DRUG THERAPY/GENETICS  HIV-1/*GENETICS
       Infant  Molecular Sequence Data  Mutation  Prospective Studies  Reverse
       Transcriptase/*GENETICS  Support, Non-U.S. Gov't  Treatment Outcome
       Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE  JOURNAL ARTICLE

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