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目的 分析成人人类免疫缺陷病毒(human immunodeficiencyvirus, HIV)/艾滋病(acquired immune deficiency syndrome, AIDS)患者接种乙型肝炎(乙肝)疫苗后免疫应答特征，探索影响HIV/AIDS患者长期免疫应答的关键因素。方法 回顾性分析2013年10月至2024年12月在重庆市巴南区人民医院、广州医科大学附属市八医院接种乙肝疫苗的HIV/AIDS患者随访资料。根据患者个人意愿，接受不同的乙肝疫苗接种方案：第一种接受3针次标准剂量的重组乙肝疫苗(0、1和6个月，20μg)，第二种接受4针次标准剂量的重组乙肝疫苗(0、1、2和6个月，20μg)。而根据患者实际接种情况，分为1针次(20μg)组、2针次(0和1个月，20μg)组、3针次(0、1和6个月，20μg)组和4针次(0、1、2和6个月，20μg)组。所有接种乙肝疫苗的患者在其疫苗接种完成后的1～6个月内进行乙型肝炎病毒表面抗体(hepatitis B surfaceantibody,HBsAb)滴度检测，并分析患者接种乙肝疫苗后1～8年的HBsAb滴度。结果 195例HIV/AIDS患者中男性172例(88.2%)，基线平均年龄(31.86±9.78)岁，CD4~+T细胞计数(414.64±166.86)/μL，所有患者接受抗反转录病毒治疗，其中158例(81.03%)基线HIV RNA低于检出限。195例HIV/AIDS患者中接种乙肝疫苗1针次44例，2针次38例，3针次100例，4针次13例。接种乙肝疫苗后6个月时免疫应答率分别为：77%(1针次)、79%(2针次)、98%(3针次)、85%(4针次)。随着时间延长，免疫应答率逐渐下降，5年后免疫应答率维持在21%～44%(1针次)、44%～67%(2针次)、82%～100%(3针次)、75%～100%(4针次)；接种3针次、4针次患者的乙肝疫苗免疫应答率显著高于1针次、2针次(P<0.001),3针次与4针次患者免疫应答率差异无统计学意义。单因素分析发现，影响长期免疫应答的因素有年龄、CD4~+T细胞计数、CD4/CD8比值、HIV RNA、6个月时免疫应答情况、基线HBsAb、乙型肝炎病毒核心抗体(hepatitis B core antibody, HBcAb)等(P<0.05)；多因素回归分析发现，接种针次、6个月时免疫应答情况和基线HBsAb是长期免疫应答的独立影响因素，即规范接种乙肝疫苗、6个月时实现免疫应答、基线HBsAb阳性，其接种后3年、5年、8年的长期免疫应答率较高。结论 成人HIV/AIDS患者规范接种、接种疫苗6个月时实现免疫应答和基线HBsAb低水平阳性是长期免疫应答的影响因素，规范接种乙肝疫苗后免疫应答率高(接种4针次与3针次乙肝疫苗免疫应答率无差异)。
Abstract：Objective To investigate the characteristics of immune responses to hepatitis B vaccination among HIV/AIDS patients and to identify key factors for achieving long-term immunity. Methods Follow-up data of HIV/AIDS patients vaccinated against hepatitis B between October 2013 and December 2024 were retrospectively analyzed. According to the vaccination regimen received, patients were divided into four groups: 1-dose(20 μg), 2-dose(20 μg at 0 and 1 month), 3-dose(20 μg at 0, 1, and 6 months), and 4-dose(20 μg at 0, 1, 2, and 6 months). All participants underwent HBsAb titer testing within 1–6 months after completing vaccination, and HBsAb titers were collected during follow-up from 1 to 8 years post-vaccination. Results A total of 195 HIV/AIDS patients were included, of whom 172(88.2%) were male. The mean baseline age was 31.86±9.78 years, and the mean CD4+ T cell count was 414.64±166.86/μL. All patients received antiretroviral therapy, and 158(81.03%) had baseline HIV RNA below the detection limit. Among the 195 patients, 44 received 1 dose, 38 received 2 doses, 100 received 3 doses, and 13 received 4 doses. The immune response rates at 6 months post-vaccination were 77%(1-dose), 79%(2-dose), 98%(3-dose), and 85%(4-dose). Over time, immune response rates gradually declined. At 5 years post-vaccination, the rates were maintained at 21%–44% in the 1-dose group, 44%–67% in the 2-dose group, 82%–100% in the 3-dose group, and 75%–100% in the 4-dose group. The immune response rates in the 3-dose and 4-dose groups were significantly higher than those in the 1-dose and 2-dose groups(P<0.001), with no statistically significant difference between the 3-dose and 4-dose groups. Univariate analysis revealed that factors influencing long-term immune response(at 3, 5, and 8 years post-vaccination) included age, CD4+ T cell count, CD4/CD8 ratio, HIV RNA, immune response status at 6 months, baseline HBsAb, and HBcAb(P<0.05). Multivariate regression analysis showed that the number of vaccine doses, immune response at 6 months, and baseline HBsAb were independent factors for long-term immune response. Conclusion HIV/AIDS patients achieve a high immune response rate after standardized hepatitis B vaccination. A higher number of doses, positive immune response at 6 months, and positive baseline HBsAb are associated with a greater probability of long-term immune response at 3, 5, and 8 years post-vaccination.
[1]Leumi S, Bigna JJ, Amougou MA, et al. Global burden of hepatitis B infection in people living with human immunodeficiency virus:A systematic review and meta-analysis[J]. Clin Infect Dis, 2020, 71(11):2799-2806. DOI:10.1093/cid/ciz1170.
[2]曹阳，周明浩，翟祥军.我国HIV感染者合并感染HBV现况[J].中华流行病学杂志，2021,42(2):327-334. DOI:10.3760/cma.j.cn112338-20200727-00987.
[3]Mallet V, Vallet-Pichard A, Pol S. The impact of human immunodeficiency virus on viral hepatitis[J]. Liver Int, 2011, 31(Suppl 1):135-139. DOI:10.1111/j.1478-3231.2010.02394.x.
[4]Mohareb AM, KouaméGM, Gabassi A, et al. Mortality in relation to hepatitis B virus(HBV)infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy[J]. J Viral Hepat, 2021, 28(4):621-629. DOI:10.1111/jvh.13461.
[5]郭朋乐，蔡卫平，陈谐捷，等.合并HBV、HCV感染对获得性免疫缺陷综合征患者死亡原因影响的研究[J].中华肝脏病杂志，2018,26(7):495-498. DOI:10.3760/cma.j.issn.1007-3418.2018.07.003.
[6]中国性病艾滋病防治协会HIV合并肝病专业委员会，广州医科大学附属市八医院.中国HIV合并HBV、HCV感染诊治专家共识[J].临床肝胆病杂志，2024,40(6):1107-1113. DOI:10.12449/JCH240607.
[7]McMahon BJ, Bulkow LR, Singleton RJ, et al. Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program[J]. Hepatology, 2011, 54(3):801-807. DOI:10.1002/hep.24442.
[8]Landrum ML, Hullsiek KH, Ganesan A, et al. Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals[J]. AIDS,2010, 24(4):545-555. DOI:10.1097/QAD.0b013e32832cd99e.
[9]胡翼云，熊燃，汤后林，等.人类免疫缺陷病毒感染儿童疫苗接种情况调查[J].中国当代儿科杂志，2019,21(3):199-202. DOI:10.7499/j.issn.1008-8830.2019.03.002.
[10]Yang T, Chen Q, Li D, et al. High prevalence of syphilis, HBV, and HCV co-infection, and low rate of effective vaccination against hepatitis B in HIV-infected patients in West China hospital[J]. J Med Virol,2018, 90(1):101-108. DOI:10.1002/jmv.24912.
[11]沈银忠.中国艾滋病诊疗指南（2024版）[J].中国病毒病杂志，2025,15(1):4-32. DOI:10.16505/j.2095-0136.2025.0001.
[12]中国疾病预防控制中心性病艾滋病预防控制中心. 2023年12月全国艾滋病性病疫情[J].中国艾滋病性病，2024,30(3):225.DOI:10.13419/j.cnki.aids.2024.03.01.
[13]Fuster F, Vargas JI, Jensen D, et al. CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients:A prospective cohort study[J]. Vaccine, 2016, 34(16):1889-1895. DOI:10.1016/j.vaccine.2016.02.055.
[14]Zhang F, Zhu H, Wu Y, Dou Z, et al. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010-12:a retrospective observational cohort study[J]. Lancet Infect Dis, 2014, 14(11):1065-1072. DOI:10.1016/S1473-3099(14)70946-6.
[15]王珍子，刘学恩，庄辉.乙型肝炎疫苗在高危人群中的应用[J].中国病毒病杂志，2015, 5(5):382-391. DOI:10.16505/j.2095-0136.2015.05.011.
[16]Tsachouridou O, Georgiou A, Naoum S, et al. Factors associated with poor adherence to vaccination against hepatitis viruses, streptococcus pneumoniae and seasonal influenza in HIV-infected adults[J]. Hum Vaccin Immunother, 2019, 15(2):295-304. DOI:10.1080/21645515.2018.1509644.
[17]Ni JD, Xiong YZ, Wang XJ, et al. Does increased hepatitis B vaccination dose lead to a better immune response in HIV-infected patients than standard dose vaccination:a meta-analysis?[J]. Int J STD AIDS,2013, 24(2):117-122. DOI:10.1177/0956462412472309.
[18]Launay O, van der Vliet D, Rosenberg AR, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1:a randomized controlled trial[J]. JAMA, 2011, 305(14):1432-1440. DOI:10.1001/jama.2011.351.
[19]Lee JH, Hong S, Im JH, et al. Systematic review and meta-analysis of immune response of double dose of hepatitis B vaccination in HIV-infected patients[J]. Vaccine, 2020, 38(24):3995-4000. DOI:10.1016/j.vaccine.2020.04.022.
[20]Kernéis S, Launay O, Turbelin C, et al. Long-term immune responses to vaccination in HIV-infected patients:a systematic review and meta-analysis[J]. Clin Infect Dis, 2014, 58(8):1130-1139. DOI:10.1093/cid/cit937.
[21]Cruciani M, Mengoli C, Serpelloni G, et al. Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients[J]. Vaccine, 2009, 27(1):17-22.DOI:10.1016/j.vaccine.2008.10.040.
[22]Cooper CL, Angel JB, Seguin I, et al. CPG 7909 adjuvant plus hepatitis B virus vaccination in HIV-infected adults achieves long-term seroprotection for up to 5 years[J]. Clin Infect Dis, 2008, 46(8):1310-1314. DOI:10.1086/533467.
[23]Kaech C, Pache I, Bürgisser P, et al. Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen[J]. J Infect, 2012, 65(2):1571-1564. DOI:10.1016/j.jinf.2012.03.009.
[24]冯永亮，常越，石璟，等.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. DOI:10.3760/cma.j.cn112338-20210319-00222.
[25]唐仁海，李畅，王继宝，等.接种H B V疫苗的HIV感染者血清抗-HBs 5年阳性率及影响因素[J].中国艾滋病性病，2022,28(6):652-657. DOI:10.13419/j.cnki.aids.2022.06.06.
[26]Landrum ML, Hullsiek KH, Ganesan A, et al. Hepatitis B vaccine responses in a large US military cohort of HIV-infected individuals:another benefit of HAART in those with preserved CD4 count[J]. Vaccine, 2009, 27(34):4731-4738. DOI:10.1016/j.vaccine.2009.04.016.
[27]Deng H, Feng Q, Wu Y, et al. Immune response to hepatitis B vaccination in human immunodeficiency virus-positive patients in China:A 2-year retrospective study[J]. J Med Virol, 2022, 94(6):2684-2693.DOI:10.1002/jmv.27523.
[28]Overton ET, Sungkanuparph S, Powderly WG, et al. Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIV-infected persons[J]. Clin Infect Dis, 2005, 41:1045-1048.DOI:10.1086/433180.
[29]Mizusawa M, perlman DC, Lucido D, et al. Rapid loss of vaccine-acquired hepatitis B surface antibody after three doses of hepatitis B vaccination in HIV-infected persons[J]. Int J STD AIDS, 2014,25(3):201-206. DOI:10.1177/0956462413495820.
[30]Kim HN, Harrington RD, van Rompaey SE, et al. Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons[J]. Int J STD AIDS, 2008, 19(9):600-604.DOI:10.1258/ijsa.2007.007197.
[31]Cornejo-Juárez P, Volkow-Fernández P, Escobedo-López K,et al.Randomized controlled trial of hepatitis B virus vaccine in HIV-1-infected patients comparing two different doses[J]. AIDS Res Ther,2006,(3):9. DOI:10.1186/1742-6405-3-9.
[32]Chaiklang K, Wipasa J, Chaiwarith R, et al. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults:a randomized,controlled trial[J]. PLoS One, 2013, 8(11):e80409. DOI:10.1371/journal.pone.0080409.
[33]Veiga AP, Casseb J, Duarte AJ. Humoral response to hepatitis B vaccination and its relationship with TCD45RA+(Naïve)and CD45RO+(Memory)subsets in HIV-1-infected subjects[J]. Vaccine,2006, 24(49-50):7124-7128. DOI:10.1016/j.vaccine.2006.06.079.
[34]Fonseca MO, Pang LW, de Paula Cavalheiro N, et al. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose[J]. Vaccine, 2005,23(22):2902-2908. DOI:10.1016/j.vaccine.2004.11.057.
[35]Kim HN, Harrington RD, Crane HM, et al. Hepatitis B vaccination in HIV-infected adults:current evidence, recommendations and practical considerations[J]. Int J STD AIDS, 2009, 20(9):595-600. DOI:10.1258/ijsa.2009.009126.
[36]Catherine FX, Piroth L. Hepatitis B virus vaccination in HIV-infected people:a review[J]. Hum Vaccin Immunother, 2017, 13(6):1-10. DOI:10.1080/21645515.2016.1277844.
[37]Pollack TM, Trang le TT, Ngo L, et al. Response to hepatitis B vaccination among HIV-infected adults in Vietnam[J]. J Virus Erad, 2016,2(2):102-106. DOI:10.1016/S2055-6640(20)30471-4.
[38]Masur H, Brooks JT, Benson CA, et al. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents:Updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America[J]. Clin Infect Dis, 2014,58(9):1308-1311. DOI:10.1093/cid/ciu094.
基本信息:
中图分类号:R186;R512.91
引用信息:
[1]聂静敏,郭朋乐,甘信蓉,等.成人HIV/AIDS患者接种乙型肝炎疫苗后免疫应答的回顾性研究[J].传染病信息,2026,39(02):122-130.
基金信息:
重庆市科卫联合项目（2024MSXM098）; 重庆市巴南区科卫联合项目（BNWJ202300150）
2026-04-30
2026-04-30