成年人类免疫缺陷病毒感染者/艾滋病患者长期抗病毒治疗后免疫功能重建分析

Immune Reconstitution in Adult HIV/AIDS Patients after Long-term Antiretroviral Therapy

背景抗逆转录病毒治疗(ART)使人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者寿命得以延长,但ART后患者长期免疫功能重建状态数据有限。近年来CD4+T淋巴细胞(简称CD4细胞):CD8+T淋巴细胞(简称CD8细胞)比值(CD4∶CD8比值)作为免疫状态评估的重要指标之一,准确了解患者ART后免疫重建情况至关重要,为临床医师管理及治疗提供可供参考的指标。目的探讨HIV感染者/AIDS患者ART后免疫功能重建情况。方法连续收集2014年7月就诊于成都市公共卫生临床医疗中心感染科门诊,并使用替诺福韦酯(TDF)+拉米夫定(3TC)+依非韦伦(EFV)方案完成ART 48个月的HIV感染者/AIDS患者98例,分析基线及ART 6、12、24、36、48个月免疫标志物变化,对观察终点CD4∶CD8比值进行相关性分析。结果基线、ART 6、12、24、36、48个月,患者CD4细胞计数、CD8细胞计数、CD4细胞恢复率、CD4∶CD8比值、CD4∶CD8比值正常化、多重T细胞重建所占比例比较,差异均有统计学意义(P<0.05)。基线CD4细胞计数≤200、201~349、≥350个/μl患者中,不同基线及各随访时间点CD4∶CD8比值比较,差异均有统计学意义(P<0.001);不同基线及各随访时间点CD4∶CD8比值正常化比较,差异均无统计学意义(P>0.05)。ART 48个月,CD4细胞计数≥500个/μl、CD4∶CD8比值正常化、多重T细胞重建分别占59.8%(58/97)、22.7%(22/97)、19.6%(19/97)。ART 48个月后,CD4∶CD8比值与基线CD4细胞计数(rs=0.269,P=0.01)、基线CD4∶CD8比值(rs=0.592,P<0.01)呈正相关,与基线CD8细胞计数(rs=-0.355,P<0.01)呈负相关,与年龄(rs=0.129,P=0.21)、HIV确诊至ART启动时间(rs=-0.141,P=0.17)、HIV-RNA病毒载量(VL)(rs=0.145,P=0.15)无关。结论长期ART成功的HIV感染者/AIDS患者仍存在免疫功能重建不良。CD4∶CD8比值与基线免疫水平相关,未来仍需大样本长时间的研究。

Background Antiretroviral therapy(ART)prolongs the life expectancy of people living with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS).However,there are limited data on the longterm immune reconstitution in such patients after ART.The ratio of CD^4+T lymphocytes(CD4 cells)to CD8+T lymphocytes(CD8 cells)has been used as a crucial marker for the assessment of immune status in recent years.Understanding post-ART immune reconstitution evaluated by immune markers(including CD4∶CD8 ratio)in such patients is of great importance,which provides clinicians with reference indicators for the management and treatment of this disease.Objective To investigate the immune reconstitution after ART in HIV/AIDS patients.Methods Participants were 98 HIV/AIDS outpatients consecutively recruited from Department of Infectious Diseases,Public Health Clinical Center of Chengdu in July 2014.All of them received 48-month ART using a regimen based on tenofovir disoproxil,lamivudine and efavirenz.Clinical data were collected,among which immune markers at baseline,and at the end of the 6th,12th,24th,36th,and 48th months of treatment were analyzed in detail.Correlation analysis was performed on the CD4∶CD8 ratio at the endpoint event.Results At baseline,and at 6,12,24,36,and 48 months after ART,CD4 cell count,CD8 cell count,CD4 cell recovery rate,CD4∶CD8 ratio,CD4∶CD8 ratio normalization rate and rate of T cells with multiple reconstitutions were all significantly different(P<0.05).CD4∶CD8 ratio differed significantly across time points(at baseline,and at 6,12,24,36,and 48 months after ART)in the subgroup of patients with baseline CD4 cell count≤200 cells/μl,201-349 cells/μl,or≥350 cells/μl(P<0.001).The rates of CD4∶CD8 ratio normalization at baseline and at each follow-up time point of post-ART showed no significant differences(P>0.05).At the end of ART,the rates of CD4 cell count≥500 cells/μl,CD4∶CD8 ratio normalization,and T cells with multiple reconstitutions were 59.8%(58/97),22.7%(22/97),and 19.6%(19/97),respectively.The CD4∶CD8 ratio at 48 months after ART was positively correlated with baseline CD4 cell count(rs=0.269,P=0.01),and baseline CD4∶CD8 ratio(rs=0.592,P<0.001),and was negatively correlated with baseline CD8 cell count(rs=-0.355,P<0.001),but was independent of age(rs=0.129,P=0.21),time from diagnosis to ART initiation(rs=-0.141,P=0.17),and viral load(rs=0.145,P=0.15).Conclusion HIV/AIDS patients with long-term ART still had poor immune reconstitution.The CD4∶CD8 ratio was related to the baseline immune level,but needs to be verified by large-sample and long-term studies.