Turriziani Ombretta, Butera Ornella, Gianotti Nicola, Parisi Saverio G, Mazzi Romualdo, Girardi Enrico, Iaiani Giancarlo, Antonelli Laura, Lazzarin Adriano, Antonelli Guido
Department of Experimental Medicine and Pathology, Virology Section, University La Sapienza, 28 00185 Rome, Italy.
AIDS. 2005 Mar 25;19(5):473-9. doi: 10.1097/01.aids.0000162335.12815.12.
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.
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.
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.
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.
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.
评估在未接受抗逆转录病毒治疗的HIV血清阳性患者中，参与某些核苷类似物磷酸化第一步的胸苷激酶（TK）和脱氧胞苷激酶（dCK）活性是否存在个体间差异。
招募了45名随机选择的未接受抗逆转录病毒治疗的HIV感染患者，以及26名无并发感染且未接受药物治疗的健康志愿者。
从静脉血中分离外周血单个核细胞（PBMC），并评估其TK和dCK活性。还对HIV感染患者的CD4 T细胞和HIV-RNA进行了检测。
HIV感染个体的TK活性存在广泛的变异性。此外，HIV感染个体PBMC中的活性显著高于健康志愿者。血清阳性患者的dCK活性显著低于健康志愿者。在HIV感染组中观察到dCK水平存在明显的个体间差异。未发现TK或dCK活性与患者的血浆病毒载量、CD4细胞计数、性别或年龄之间存在相关性。
HIV感染个体的PBMC中TK和dCK活性存在明显的个体间差异，而健康志愿者中不存在，这表明在药物激活中起关键作用的酶活性在不同患者之间可能有很大差异。此外，HIV感染个体的TK表达高于健康志愿者。更好地了解导致这种变异性的病毒或细胞因素，以及它们对抗逆转录病毒治疗反应的影响，可能有助于优化HIV感染患者的管理。
