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M94A0343.TXT
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1994-10-08
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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).