Lucignani Giovanni, Orunesu Eva, Cesari Miriam, Marzo Katia, Pacei Michela, Bechi Giulia, Gori Andrea, Gaito Sabrina, Clerici Mario, Chiti Arturo
Institute of Radiological Sciences, University of Milan, San Paolo Hospital, Milan, Italy.
Eur J Nucl Med Mol Imaging. 2009 Apr;36(4):640-7. doi: 10.1007/s00259-008-1023-7. Epub 2008 Dec 11.
To characterise tissue sites of immune activation and HIV replication we performed FDG-PET in ART-treated and ART-naive HIV-infected individuals. Specific aims were to establish whether HIV-infected patients can be differentiated on the basis of the detection of specific locations of viral replication, even in the presence of an apparently optimal immunovirological response to ART, and whether these FDG-PET findings can be related to immunovirological variables and AIDS history status.
Patients were divided into five groups as follows: subgroup A1 (full responders, n = 8): current ART treatment, CD4+ T lymphocytes >500/mL, viral load <50 copies/mL; subgroup A2 (full responders, n = 5): same criteria as A-1, but with a previous history of AIDS; subgroup A3 (immunological non responders, n = 5): current ART treatment, viral load <50 copies/mL, low CD4+ T lymphocytes (<200/mL); group B (virological non responders, n = 2): current ART treatment, CD4+ T lymphocytes around 500/mL, viral load >50,000 copies/mL; group C (ART-naïve, n = 5): no current or previous ART treatment, increased viral load.
PET images revealed different patterns of FDG uptake. All ART-treated patients with either suppressed (<50 copies/mL; Group A) or high viremia (group B) showed a normal pattern of FDG uptake. On the contrary, the ART-naïve subjects with high viraemia (group C) displayed multiple foci of increased glucose metabolism in the lymph nodes. In the ART-naïve subjects, FDG uptake, apparently related to viraemia level, was observed in the upper torso mainly in the axillary nodes bilaterally in patients with viraemia below 100,000 copies/mL; in those with viraemia higher than 100,000 copies/mL, FDG uptake was also observed in the inguinal lymph nodes.
The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.
为了明确免疫激活和HIV复制的组织部位，我们对接受抗逆转录病毒治疗（ART）和未接受ART的HIV感染者进行了FDG-PET检查。具体目标是确定即使在对ART有明显最佳免疫病毒学反应的情况下，是否可以根据病毒复制的特定位置检测来区分HIV感染患者，以及这些FDG-PET检查结果是否与免疫病毒学变量和艾滋病病史状态相关。
患者分为以下五组：A1亚组（完全缓解者，n = 8）：目前接受ART治疗，CD4+ T淋巴细胞>500/mL，病毒载量<50拷贝/mL；A2亚组（完全缓解者，n = 5）：与A1组标准相同，但有艾滋病病史；A3亚组（免疫无反应者，n = 5）：目前接受ART治疗，病毒载量<50拷贝/mL，CD4+ T淋巴细胞低（<200/mL）；B组（病毒学无反应者，n = 2）：目前接受ART治疗，CD4+ T淋巴细胞约500/mL，病毒载量>50,000拷贝/mL；C组（未接受ART者，n = 5）：目前或既往未接受ART治疗，病毒载量升高。
PET图像显示了不同的FDG摄取模式。所有接受ART治疗且病毒抑制（<50拷贝/mL；A组）或病毒血症高（B组）的患者均显示出正常的FDG摄取模式。相反，未接受ART且病毒血症高的受试者（C组）在淋巴结中显示出多个葡萄糖代谢增加的病灶。在未接受ART的受试者中，FDG摄取显然与病毒血症水平相关，病毒血症低于100,000拷贝/mL的患者主要在上半身双侧腋窝淋巴结中观察到FDG摄取；病毒血症高于100,000拷贝/mL的患者，在腹股沟淋巴结中也观察到FDG摄取。
在我们的研究中，未接受ART的患者中CD8+/CD38+/RO+ T细胞百分比（与艾滋病进展密切相关的标志物，独立于CD4+ T淋巴细胞）与FDG-PET阳性之间出现相关性，这是一项新发现，似乎赋予了FDG摄取预后价值。FDG摄取与对ART的反应密切相关，与既往是否有艾滋病诊断无关。值得注意的是，在分类为免疫反应者和非反应者的接受ART治疗的受试者之间未观察到差异。此处的数据表明，在进行ART治疗时，FDG摄取与免疫变量无关。这证明了免疫和FDG测量的互补性。FDG摄取是疾病状态的敏感标志物，其与CD8+/CD38+/CD45RO+ T细胞的关系表明它可被视为疾病状态的标志物。接受ART治疗的患者中FDG摄取与免疫变量缺乏相关性值得进一步研究。
