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HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in children treated with zidovudine. 1994

N Principi, and P Marchisio, and M P De Pasquale, and E Massironi, and R Tornaghi, and T Vago
Pediatric Department (IV), University of Milan, Italy.

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. METHODS A prospective, open study. METHODS A University Pediatric Department. 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012194 RNA-Directed DNA Polymerase An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49. DNA Polymerase, RNA-Directed,RNA-Dependent DNA Polymerase,Reverse Transcriptase,RNA Transcriptase,Revertase,DNA Polymerase, RNA Directed,DNA Polymerase, RNA-Dependent,RNA Dependent DNA Polymerase,RNA Directed DNA Polymerase

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