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 stav udine (d4T) to the corresponding monophosphate form. In HIV-1-infected pati ents, treated with combination therapy including one of these compounds for more than 1 year, enzymatic activity of TK1 in peripheral blood mononuclea r 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 wit h decreased CD4 cell count and high viral load. Furthermore, TK1 activity d iffers between HIV-1-infected individuals treated for more than 6 months (1 3.5 pmol/mg/h) compared to patients treated for less than 6 months (28.1 pm ol/mg/h; p < 0.05) with chemotherapeutic agents including thymidine analogs . The results demonstrate that TK1 deficiency in PBMC of HIV-1 infected pat ients may develop due to continuous treatment with thymidine analogs and co rrelates with a more progressed stage of disease expressed as diminished CD 4 cell count and increased viral load.