The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5’-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens.

嘌呤类似物替诺福韦和阿巴卡韦是肌苷5'-三磷酸焦磷酸水解酶（ITPase）潜在底物的前体。在这里，我们调查了联合抗逆转录病毒疗法（cART）对人类免疫缺陷病毒（HIV）感染过程中ITPase活性和ITPA基因型与不良事件（AEs）发生的关系。在393名成人HIV血清阳性患者中，不良事件定义为导致终止cART方案的事件。ITPase活性≥4mmol IMP / mmol Hb /小时被认为是正常的。通过测试两个ITPA来确定ITPA基因型多态性：c.94C> A（p.Pro32Thr，rs1127354）和c.124 + 21A> C（rs7270101）。Logistic回归分析确定了发展中的AE的优势比。在含替诺福韦的方案中，ITPase活性降低与AE较少（p = 0.01）和方案持续时间较长（p = 0.001）相关。相反，在含阿巴卡韦的方案中，ITPase活性降低与更多的AE相关（粗略p = 0.02）和由于AEs引起的药物转换增加（p = 0.03）。在含有替诺福韦的方案中，ITPA基因型wt / wt与AE发生的增加显着相关。ITPase活性降低似乎可以防止含有替诺福韦的cART中发生AE，而与含有abacavir的治疗方案中AE的增加有关。