Activity of Cellular Thymidine Kinase 1 in PBMC of HIV-1-Infected Patients: Novel Therapy Marker

Abstract

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.