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M9620657.TXT
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1996-02-26
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Document 0657
DOCN M9620657
TI Emergence and clinical relevance of mutations associated with zidovudine
resistance in asymptomatic HIV-1 infected patients.
DT 9602
AU Calderon EJ; Torres Y; Medrano FJ; Luque F; Larder B; Rey C;
Sanchez-Quijano A; Lissen E; Leal M; Department of Internal Medicine,
Virgen del Rocio University; Hospital, Seville, Spain.
SO Eur J Clin Microbiol Infect Dis. 1995 Jun;14(6):512-9. Unique Identifier
: AIDSLINE MED/96082795
AB The dynamics leading to the emergence of a zidovudine-resistant mutation
at codon 215 of the reverse transcriptase coding region was investigated
in a cohort of HIV-infected individuals who received early zidovudine
therapy. Clinical implications and the role of the resistance mutation
at codon 41 were also assessed. Thirty-eight initially asymptomatic
HIV-infected patients with a CD4+ cell count above 400 cells/mm3 were
followed for a mean period of 121 weeks (20 received zidovudine and 18
matching placebo). Specific mutations in the HIV-1 reverse transcriptase
coding region conferring resistance to zidovudine were detected using a
selective polymerase chain reaction. During the follow-up period a
mutation at codon 215 was detected in eight (40%) of the individuals in
the zidovudine group, and in two of these eight subjects, a mutation at
codon 41 was found. During the study, disease progression occurred in
seven of the eight (88%) patients with a mutation at codon 215, compared
with 7 of 18 (39%) patients assigned to the placebo group and 3 of the
12 (25%) patients receiving zidovudine treatment who did not develop a
215-mutant strain (p < 0.05). At entry, none of the patients harbored
MT-2 tropic virus. Therefore, the emergence of a zidovudine-resistant
mutation at codon 215 is associated with subsequent disease progression
in asymptomatic HIV-infected patients who receive zidovudine
monotherapy. This association suggests that the mutation at codon 215 is
involved in a loss of therapeutic efficacy and, therefore, patients
should be monitored during treatment with zidovudine.
DE Adult Antiviral Agents/*THERAPEUTIC USE Base Sequence Codon Cohort
Studies CD4 Lymphocyte Count Disease Progression Double-Blind Method
Drug Resistance, Microbial/GENETICS Female Human HIV
Seropositivity/*DRUG THERAPY/IMMUNOLOGY HIV-1/*DRUG EFFECTS/GENETICS
Male Molecular Sequence Data *Mutation Polymerase Chain Reaction
RNA-Directed DNA Polymerase Support, Non-U.S. Gov't
Zidovudine/*THERAPEUTIC USE CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED
CONTROLLED TRIAL
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).