文章摘要
冯永亮,常越,石璟,蓝光华,鲁鸿燕,向绍密,王富珍,王素萍.不同CD4+T淋巴细胞水平的HIV感染者乙型肝炎疫苗免疫效果及持久性研究[J].中华流行病学杂志,2021,42(9):1559-1565
不同CD4+T淋巴细胞水平的HIV感染者乙型肝炎疫苗免疫效果及持久性研究
Immunization effect and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell levels
收稿日期:2021-03-19  出版日期:2021-09-27
DOI:10.3760/cma.j.cn112338-20210319-00222
中文关键词: 艾滋病病毒;乙型肝炎疫苗;CD4+T淋巴细胞;免疫原性;持久性
英文关键词: HIV;Hepatitis B vaccine;CD4+T cells;Immunogenicity;Persistence
基金项目:国家科技重大专项(2018ZX10721202,2012ZX10002001)
作者单位E-mail
冯永亮 山西医科大学公共卫生学院流行病学教研室, 太原 030001
山西医科大学临床流行病学与循证医学中心, 太原 030001 
 
常越 山西医科大学公共卫生学院流行病学教研室, 太原 030001
山西医科大学临床流行病学与循证医学中心, 太原 030001 
 
石璟 山西医科大学公共卫生学院流行病学教研室, 太原 030001
山西医科大学临床流行病学与循证医学中心, 太原 030001 
 
蓝光华 广西壮族自治区疾病预防控制中心艾滋病防制所, 南宁 530028  
鲁鸿燕 广西壮族自治区疾病预防控制中心艾滋病防制所, 南宁 530028  
向绍密 宁明县疾病预防控制中心 532500  
王富珍 中国疾病预防控制中心免疫规划中心, 北京 100050  
王素萍 山西医科大学公共卫生学院流行病学教研室, 太原 030001
山西医科大学临床流行病学与循证医学中心, 太原 030001 
supingwang@sxmu.edu.cn 
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中文摘要:
      目的 分析HIV感染者CD4+T淋巴细胞(CD4)水平对乙肝疫苗免疫应答的影响,探讨不同CD4水平的HIV感染者乙肝疫苗免疫效果及其持久性,为优化HIV感染者乙肝疫苗免疫策略提供理论支持。方法 以2014年广西壮族自治区CDC和宁明县CDC管理的参加0-1-6月20μg和60μg乙肝疫苗接种随机对照试验的182名HIV感染者为研究对象,在首针接种后6个月和全程接种后1个月、6个月、1年和3年时,采集研究对象静脉血5 ml,并采用化学发光微粒子免疫分析方法定量检测乙肝表面抗体(抗-HBs)。本研究在既往研究基础上,着重分析不同CD4水平下乙肝疫苗接种后的免疫效果及持久性。结果 CD4<350个/μl的HIV感染者乙肝疫苗全程接种后1个月时,抗-HBs几何平均浓度(GMC)为442.50 mIU/ml,抗-HBs阳性率为71.05%(27/38),强阳性率为44.74%(17/38),明显低于CD4 ≥ 350个/μl者[583.90 mIU/ml、92.13%(117/127)和77.95%(99/127)](P<0.05);多因素分析结果显示,控制混杂因素后,CD4<350个/μl者乙肝疫苗抗-HBs阳性的概率是CD4 ≥ 350个/μl者的0.14倍(95% CI:0.03~0.62),CD4水平较低是乙肝疫苗无应答的危险因素。全程接种后6个月到3年时,CD4<350个/μl者抗-HBs GMC(195.00~27.55 mIU/ml比300.10~45.81 mIU/ml)、阳性率(56.67%~36.67%比78.57%~51.58%)和强阳性率(33.33%~6.67%比44.64%~15.79%)不同程度下降,且均低于CD4 ≥ 350个/μl者。结论 CD4<350个/μl的HIV感染者乙肝疫苗无应答风险高,免疫持久性较差,应定期监测HIV感染者抗-HBs水平,并特别关注CD4<350个/μl者,抗-HBs阴性时应尽早全程及加强接种乙肝疫苗。
英文摘要:
      Objective To explore the immunogenicity and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell (CD4) levels, and analyze the influence effect of CD4 levels on immunization response. Methods A total of 182 HIV-infected patients who participated in a randomized controlled trial of 20 μg and 60 μg hepatitis B vaccination at month 0, 1, and 6 in 2014 by Guangxi Zhuang Atonomous Region CDC and Ningming county CDC were surveyed. Six months later after the first dose and 1 month, 6 months, 1 year, and 3 years later after the full course of the vaccination, 5 ml of the venous blood of the patients was collected, and the anti-HBs was detected by Chemiluminescent Microparticle Immunoassay (CMIA). On the basis of previous studies, this study focused on analyzing the immunogenicity and persistence of hepatitis B vaccine under different CD4 levels. Results One month later after the whole course of hepatitis B vaccination, the anti-HBs geometric mean concentration (GMC), anti-HBs positive rate (≥ 10 mIU/ml) and strong positive rate (≥ 100 mIU/ml) in HIV patients with CD4 <350 cells/μl were 442.50 mIU/ml, 71.05% (27/38) and 44.74% (17/38), respectively, which were significantly lower than those HIV-infected patients with CD4 ≥ 350 cells/μl[583.90 mIU/ml, 92.13% (117/127) and 77.95% (99/127)] (P<0.05). After controlling the confounding factors, the probability of being anti-HBs positive induced by hepatitis B vaccine in patients with CD4 <350 cells/μl was 0.14 times higher than in those with CD4 ≥ 350 cells/μl (95%CI:0.03-0.62), and patients with CD4 <350 cells/μl had higher risk of no response. From 6 months to 3 years after the whole course of the vaccination, the anti-HBs GMC (195.00-27.55 mIU/ml vs. 300.10-45.81 mIU/ml), the positive rate (56.67%-36.67% vs. 78.57%-51.58%) and the strong positive rate (33.33%-6.67% vs.44.64%-15.79%) in patients with CD4 <350 cells/μl gradually declined, lower than the levels in those with CD4 ≥ 350 cells/μl.Conclusions HIV-infected patients with CD4 <350 cells/μl have high risk of no response to hepatitis B vaccination and poor immune persistence. It is necessary to strengthen the anti-HBs monitoring in HIV-infected patients, with special attention to those with CD4 <350 cells/μl. When anti-HBs is negative, hepatitis B vaccine should be injected as early as possible.
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