Lack of reduction of thymidine kinase activity in stavudine-treated hiv-infected patients

Ombretta Turriziani, Nicola Gianotti, Federica Bambacioni, Paolo Emilio Manconi, Adriano Lazzarin, Guido Antonelli

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It has been demonstrated that prolonged in vivo or in vitro treatment with some nucleosides analogs may favor the selection of cells with a reduced activity of enzymes involved in the phosphorylation of these drugs leading to a reduced sensitivity to their antiretroviral action. The aim of this study was to evaluate the effect, in vivo, of zidovudine and stavudine treatment on thymidine kinase (TK) activity. The results obtained showed that TK levels in PBMC from naive patients and stavudine-treated patients did not significantly differ (naive TK = 4.16 ± 1.19 U/mg protein; stavudine TK = 3.65 ± 1.73 U/mg protein; p = 0.42), suggesting that the treatment with this nucleoside analog is not associated to a defect of TK activity. On the contrary, PBMC from zidovudine-treated patients showed a significant reduction in TK activity compared to naive patients (naive TK = 4.16 ± 1.19 U/mg protein; zidovudine TK = 2.70 ± 1.54; p = 0.014. Although the clinical significance of these results has to be established, we can speculate that stavudine and zidovudine, which are presumably phosphorylated by the same cellular kinases, might display a different ability to in vivo select cells with a resistant phenotype.

Original languageEnglish
Pages (from-to)701-703
Number of pages3
JournalAIDS Research and Human Retroviruses
Issue number7
Publication statusPublished - Jul 2004

ASJC Scopus subject areas

  • Immunology
  • Virology


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