抗巨细胞病毒治疗对获得性免疫缺陷综合征合并巨细胞病毒血症患者外周血凋亡相关因子水平的影响

Effect of anti-cytomegalovirus therapy on blood levels of apoptosis-related factors in patients with AIDS and cytomegalovirus viremia

摘要:

目的  探讨抗巨细胞病毒（CMV）治疗对获得性免疫缺陷综合征（简称艾滋病）合并CMV血症患者的外周血凋亡相关因子水平的影响。方法  选取2014年1月1日～12月31日中国医科大学附属第一医院确诊住院的外周血CMVIgG阳性的男性艾滋病患者（CD4+ T<200个/μl）共34例（排除合并CMV视网膜炎者）。非随机对照分为3组，阴性CMV血症组（n =11）、阳性CMV血症非抗CMV组（n =11）、阳性CMV血症抗CMV组（n =12）。同时设立性别、年龄匹配的12例健康人做对照。同时全部入组患者于第3周末接受高效抗逆转录病毒治疗。在随访12月末时，评价各组CD4+T细胞计数、CMV视网膜炎的发生率；评价外周血凋亡相关因子浓度的变化及组间差异。结果  与健康对照比较，艾滋病患者Fas、FasL、TRAIL、TNF-α水平升高（t =-3.369、-2.683、-4.321和-5.321，P =0.012、0.033、0.009和0.003），而Bcl-2水平降低（t =-4.321，P =0.001）。基线时3组年龄、HIVRNA载量、CD4+T细胞计数、WHO临床分期差异无统计学意义；非抗CMV组与抗CMV组CMVDNA载量差异无统计学意义。与非抗CMV组比较，抗CMV组与阴性CMV血症组12个月时CD4+T细胞计数升高（F =4.260，P =0.013和0.020）；外周血Bcl-2（F =3.621，P =0.009和0.006）、FasL（F =2.891，P = 0.024和0.002）、TNF-α浓度降低（F =4.912，P =0.003和0.001）；而抗CMV组与阴性CMV血症组组间未见差异。与基线水平比较，艾滋病患者随访12个月时Fas、FasL和TRAIL水平下降（t =2.579、2.194和2.274，P =0.015、0.035和0.030）。观察期内无CMV视网膜炎发生，无死亡病例，无HIV病毒学反弹发生。结论  抗CMV治疗促进艾滋病合并CMV血症患者的CD4+T细胞计数增长，这可能与外周血Bcl-2、FasL和TNF-α浓度降低有关。此外，高效抗逆转录病毒治疗本身也可以降低Fas、FasL和TRAIL水平。

Abstract:

Objective To explore the effect of anti-cytomegalovirus therapy on the blood levels of apoptosis-related factors of patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) viremia. Methods The study was carried out in the 34 male hospitalized patients who were newly diagnosed as AIDS in the First Affiliated Hospital of China Medical University from January 1, 2014 to December 31, 2014. The patients were divided into CMV viraemia negative group (n = 11), CMV viraemia positive non-treatment group (n = 11), and CMV viraemia positive treatment group (n = 12). Meanwhile 12 healthy controls were included.  The baseline age, CMV-DNA, HIV-RNA, CD4+T cells and World Health Organization clinical stages were evaluated in the groups. Patients received highly active antiretroviral therapy at the end of the 3rd week. CD4+T cell count, the incidence of CMV retinitis and the blood levels of apoptosis-related factors were evaluated at the end of the 12th month. Results Compared with the health controls, the levels of Fas, FasL, TRAIL and TNF-α increased in the patients with AIDS (t = -3.369, -2.683, -4.321 and -5.321; P = 0.012, 0.033, 0.009 and 0.003 respectively), while the level of Bcl-2 was lowered (t = -4.321, P = 0.001). There was no significant difference in the baseline age, HIV-RNA load, CD4+T cell count or WHO clinical stages among the three disease groups. There was no difference in the CMV-DNA load between the CMV non-treatment group and the CMV treatment group. At the end of the 12th month, compared with the CMV non-treatment group, the CD4+T cell count increased (F = 4.260, P = 0.013 and 0.020), lower levels of Bcl-2 (F = 3.621, P = 0.009 and 0.006), FasL (F = 2.891, P = 0.024 and 0.002) and TNF-α (F = 4.912, P = 0.003 and 0.001) were found in both the CMV treatment and CMV negative groups; while there were no differences between the CMV treatment group and the CMV negative group. Compared with levels at baseline, the levels of Fas, FasL and TRAIL were decreased at the end of the 12th month in the AIDS patients (t = 2.579, 2.194 and 2.274; P = 0.015, 0.035 and 0.030). There was no occurrence of CMV retinitis, death or virological rebound. Conclusions Anti-cytomegalovirus therapy is beneficial to the increment of CD4+T cells in patients with AIDS and CMV viremia, which may be due to obvious decrease in blood levels of Bcl-2, FasL and TNF-α. Furthermore, the levels of Fas, FasL and TRAIL are also decreased after highly active antiretroviral therapy.