Saracino Annalisa, Bruno Giuseppe, Scudeller Luigia, Volpe Anna, Caricato Pierluigi, Ladisa Nicoletta, Monno Laura, Angarano Gioacchino
1 Clinic of Infectious Diseases, University of Bari , Bari, Italy .
AIDS Res Hum Retroviruses. 2014 Dec;30(12):1178-84. doi: 10.1089/aid.2014.0080.
In HIV-infected patients a low CD4:CD8 ratio can persist despite CD4 recovery with long-term antiretroviral treatment (ART). As CD4:CD8 inversion is considered a marker of immune-senescence, we aimed to assess if it was associated with the chronic inflammation state in aging patients with HIV. A total of 112 patients with a >15 year history of HIV infection and ART were included, 85 of whom were suppressed. All subjects were tested for interleukin (IL)-6, high-sensitivity (hs)-PCR, and D-dimer levels. Complete clinical, therapeutic, and hematochemical data were retrieved. Coreceptor tropism based on HIV-DNA gp120 genotyping was also available within the past 6 months. A progressive increase in the CD4:CD8 ratio over time was observed without reaching a plateau. Based on the CD4:CD8 ratio at the time of testing, patients were classified into group A (normal ratio ≥0.9) and group B (<0.9). A normal ratio was observed in 37% of patients. Variables associated with an inverted CD4:CD8 ratio were older age, nadir CD4, and detectable HIV viremia. No association between HIV subtype, coreceptor tropism, cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) coinfections and CD4:CD8 ratio was observed. Group B patients showed a trend for a higher frequency of diabetes and hypertriglyceridemia compared to group A patients, but they did not differ in IL-6, hs-PCR, and D-dimer levels or in frequency of severe non-AIDS-associated events. In conclusion, CD4:CD8 ratio normalization occurs rarely, even after several years of ART. Chronic inflammation in patients aging with HIV does not seem to be directly dependent on the CD4:CD8 ratio. However, the persistent immune dysregulation expressed by a CD4:CD8 inversion might be linked to a higher risk of non-AIDS events, especially metabolic disorders.
在接受长期抗逆转录病毒治疗（ART）且CD4已恢复的HIV感染患者中，CD4:CD8比值仍可能持续偏低。由于CD4:CD8倒置被认为是免疫衰老的一个标志，我们旨在评估其是否与老年HIV患者的慢性炎症状态相关。总共纳入了112例有超过15年HIV感染和ART病史的患者，其中85例病毒得到抑制。对所有受试者检测白细胞介素（IL）-6、高敏（hs）-PCR和D-二聚体水平。收集完整的临床、治疗和血液生化数据。过去6个月内也有基于HIV-DNA gp120基因分型的共受体嗜性数据。观察到CD4:CD8比值随时间逐渐升高，但未达到平台期。根据检测时的CD4:CD8比值，患者被分为A组（正常比值≥0.9）和B组（<0.9）。37%的患者观察到正常比值。与CD4:CD8比值倒置相关的变量有年龄较大、CD4最低点以及可检测到的HIV病毒血症。未观察到HIV亚型、共受体嗜性、巨细胞病毒（CMV）、乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）合并感染与CD4:CD8比值之间存在关联。与A组患者相比，B组患者糖尿病和高甘油三酯血症的发生率有升高趋势，但在IL-6、hs-PCR和D-二聚体水平或严重非艾滋病相关事件的发生率方面并无差异。总之，即使经过数年的ART治疗，CD4:CD8比值正常化的情况也很少见。老年HIV患者的慢性炎症似乎并不直接依赖于CD4:CD8比值。然而，CD4:CD8倒置所表现出的持续免疫失调可能与非艾滋病事件尤其是代谢紊乱的较高风险有关。
