不同CD4<sup>+</sup>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

冯永亮; 常越; 石璟; 蓝光华; 鲁鸿燕; 向绍密; 王富珍; 王素萍

Abstract

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].Chinese journal of Epidemiology,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

Received:March 19, 2021

DOI：10.3760/cma.j.cn112338-20210319-00222

KeyWord: 艾滋病病毒乙型肝炎疫苗 CD4⁺T淋巴细胞免疫原性持久性

English Key Word: HIV Hepatitis B vaccine CD4⁺T cells Immunogenicity Persistence

FundProject:国家科技重大专项（2018ZX10721202，2012ZX10002001）

Author Name	Affiliation	E-mail
Feng Yongliang	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Chang Yue	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Shi Jing	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Lan Guanghua	Institute of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning 530028, China
Lu Hongyan	Institute of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning 530028, China
Xiang Shaomi	Ningming County Center for Disease Control and Prevention, Ningming 532500, China
Wang Fuzhen	Department of National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing 100050, China
Wang Suping	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China	supingwang@sxmu.edu.cn

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Abstract:

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。

English Abstract:

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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