title: Thymidine kinase and deoxycytidine kinase activity in mononuclear cells from antiretroviral-naive HIV-infected patients.
abstract: OBJECTIVE
  To evaluate whether an inter-individual variability in the activity of thymidine kinase (TK) and deoxycytidine kinase (dCK), which are involved in the first step of phosphorylation of some nucleoside analogues, exists in antiretroviral-naive, HIV-seropositive patients.
  
  
  METHODS
  Forty-five randomly selected antiretroviral-naive HIV-infected patients were recruited, together with 26 healthy volunteers with no concurrent infection and under no pharmacological treatment.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) were isolated from venous blood and their TK and dCK activities evaluated. CD4 T cells and HIV-RNA were measured in HIV-infected patients, too.
  
  
  RESULTS
  There was a broad range of variability in TK activity in HIV-infected individuals. Furthermore, the activity in PBMC was significantly higher in HIV-infected individuals than in healthy volunteers. dCK activity in seropositive patients was significantly lower than in healthy volunteers. A marked inter-individual variability in dCK levels was observed in the HIV-infected group. No correlations were found between TK or dCK activities and plasma viral load, CD4 cell count, sex or age of patients.
  
  
  CONCLUSIONS
  A marked range of inter-individual variability of TK and dCK activities in PBMC exists in HIV-infected individuals but not in healthy volunteers, indicating that the activity of enzymes with key roles in drug activation could vary greatly from one patient to another. Furthermore, TK expression is greater in HIV-infected individuals than in healthy volunteers. Better understanding of the viral or cellular factors that contribute to this variability, as well as their effect on responses to antiretroviral treatment, may aid optimization of the management of HIV-infected patients.
authors.affiliation: Department of Experimental Medicine and Pathology, Virology Section, University La Sapienza, 28 00185 Rome, Italy.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Turriziani
authors.forename: Ornella
authors.initials: O
authors.lastname: Butera
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Saverio G
authors.initials: SG
authors.lastname: Parisi
authors.forename: Romualdo
authors.initials: R
authors.lastname: Mazzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Iaiani
authors.forename: Laura
authors.initials: L
authors.lastname: Antonelli
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000378:metabolism; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism*; D015215:Zidovudine / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D015215:Zidovudine; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase; D013936:Thymidine