A Mutation in Human Immunodeficiency Virus Reverse Transcriptase and Decline in CD4 Lymphocyte Numbers in Long-Term Zidovudine Recipients

A nested polymerase chain reaction assay was used to define the sequence of a specific codon, amino acid 215, of the human immunodeficiency virus (HIV) pol gene in DNA from peripheral blood mononuclear cells (PBMC) and viral RNA from serum from 38 patients treated with zidovudine for ⩾2 years. After...

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Bibliographic Details
Published in:The Journal of infectious diseases 1993-03, Vol.167 (3), p.526-532
Main Authors: Kozal, Michael J., Shafer, Robert W., Winters, Mark A., Katzenstein, David A., Merigan, Thomas C.
Format: Article
Language:English
Subjects:
AIDS
AIDS/HIV
Biological and medical sciences
CD4-Positive T-Lymphocytes - drug effects
Codon - genetics
Codons
DNA
DNA, Viral - blood
Drug Resistance - genetics
Fundamental and applied biological sciences. Psychology
Genes, pol - drug effects
Genetic mutation
Genetics
HIV
HIV - enzymology
HIV - genetics
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - microbiology
Humans
Leukocyte Count - drug effects
Longitudinal Studies
Lymphocytes
Major Articles
Microbiology
Point Mutation
Polymerase Chain Reaction
Proviruses - drug effects
Proviruses - genetics
RNA
RNA, Viral - blood
RNA, Viral - drug effects
RNA-Directed DNA Polymerase - genetics
Viral RNA
Virology
Viruses
Zidovudine - pharmacology
Zidovudine - therapeutic use
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Summary:A nested polymerase chain reaction assay was used to define the sequence of a specific codon, amino acid 215, of the human immunodeficiency virus (HIV) pol gene in DNA from peripheral blood mononuclear cells (PBMC) and viral RNA from serum from 38 patients treated with zidovudine for ⩾2 years. After treatment for a mean of 34 months, 17 patients with sequences with a codon 215 mutation had a mean 50% decrease in CD4 cells, compared with 21 patients with sequences wild-type at codon 215, who had a mean 11% increase in CD4 cells (P < .0001). Patients with a mutation at 215 had a ninefold higher provirus burden in PBMC. Detection of the codon 215 mutation in plasma viral RNA preceded detection of the mutation in DNA from PBMC and decline in CD4 cells. The appearance of a mutation at codon 215 in the HIV reverse transcriptase gene in patients receiving zidovudine may be a marker for impending immunologic decline.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/167.3.526