Activity of cellular thymidine kinase 1 in PBMC of HIV-1-infected patients: novel therapy marker.
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.
Gröschel
B
B
Institute of Medical Virology, Johann Wolfgang Goethe University, Frankfurt, Germany. Groeschel@em.uni-frankfurt.de
Miller
V
V
Doerr
H W
HW
Cinatl
J
J
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D018119:Stavudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013937:Thymidine Kinase / Q000032:analysis / Q000378:metabolism*; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015415:Biomarkers; D015215:Zidovudine; D018119:Stavudine; D013937:Thymidine Kinase; C092717:thymidine kinase 1