ISSN:
1439-0973
Keywords:
Key Words Cellular resistance
;
TK1 activity
;
HIV-1
;
Zidovudine
;
Antiretroviral therapy
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Cellular cytoplasmatic thymidine kinase 1 (TK1) catalyzes the intracellular phosphorylation of anti-HIV-1 nucleoside analogs zidovudine (AZT) and stavudine (d4T) to the corresponding monophosphate form. In HIV-1-infected patients, treated with combination therapy including one of these compounds for more than 1 year, enzymatic activity of TK1 in peripheral blood mononuclear cells (PBMC) was determined by radioactive assay. TK1 activity in PBMC of HIV-1-infected patients correlated with CD4 cell count (r = 0.4, p 〈 0.05) and HIV-1 RNA copy number (r = 0.4, p 〈 0.05), being lower in patients with decreased CD4 cell count and high viral load. Furthermore, TK1 activity differs between HIV-1-infected individuals treated for more than 6 months (13.5 pmol/mg/h) compared to patients treated for less than 6 months (28.1 pmol/mg/h; p 〈 0.05) with chemotherapeutic agents including thymidine analogs. The results demonstrate that TK1 deficiency in PBMC of HIV-1 infected patients may develop due to continuous treatment with thymidine analogs and correlates with a more progressed stage of disease expressed as diminished CD4 cell count and increased viral load.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s150100070037
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