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
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
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DOI：
10.1001/jama.2011.351
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发表时间：
2011-04-13
影响因子：
120.7
通讯作者：
Carrat, Fabrice
中科院分区：
文献类型：
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作者：
Launay, Odile;van der Vliet, Diane;Carrat, Fabrice
背景 人类免疫缺陷病毒 1 (HIV-1) 感染患者需要比标准乙型肝炎疫苗方案更具免疫原性的替代方案。目的 比较 4 种肌内双剂量方案和 4 种皮内低剂量方案与标准乙型肝炎疫苗方案的安全性和免疫原性。设计、设置和参与者 2007 年 6 月 28 日至 10 月期间进行的一项开放标签、多中心、1:1:1 平行组随机试验2008 年 2 月 23 日（最后一次患者就诊日期，2009 年 7 月 3 日）在法国 33 个中心，患者参加了法国国家艾滋病和病毒性肝炎研究机构对乙型肝炎病毒 (HBV) 血清阴性且 CD4 细胞计数超过 200 个细胞/μL 的 HIV-1 感染成人进行的试验。 干预 患者被随机分配接受 3 次肌肉注射标准剂量（20 μg）的重组蛋白第 0、4 和 24 周时接种 HBV 疫苗（IM20 x 3 组，n=145）；第0、4、8、24周肌内双倍剂量（40μg[2次注射20μg]）重组乙肝疫苗（IM40×4组，n=148）；或在第 0、4、8 和 24 周皮内注射 4 次低剂量（4 μg [20 μg 的 1/5]）重组 HBV 疫苗（ID4 x 4 组，n=144）。 主要结果指标 第 28 周时的应答者百分比，定义为接受至少 1 剂疫苗的患者中乙型肝炎表面抗体（抗 HBs）至少为 10 mIU/mL疫苗。在第 28 周最后一次随访时缺少抗 HBs 滴度测量的患者被视为主要（功效）分析中的无反应者。 结果 总共 437 名患者被随机分配到 3 个研究组，其中 11 名患者未接受任何疫苗。其中，396 人在第 28 周时具有可用的抗 HBs 滴度。第 28 周时，IM20 x 3 组 (n=91) 中的应答者百分比为 65%（95% 置信区间 [CI]，56%-72%），IM40 x 4 组 (n=119) 中的应答者百分比为 82%（95% CI，77%-88%）（P < .001 vs IM20 x 3 组），ID4 x 4 组（n=108）为 77%（95% CI，69%-84%）（与 IM20 x 3 组相比，P=0.02）。没有观察到安全信号，并且对 CD4 细胞计数或病毒载量没有影响。 结论 在成人 HIV-1 患者中，与标准 HBV 疫苗方案相比，4 肌内双剂量方案和 4 皮内低剂量方案均改善了血清学反应。
Context Alternative schedules more immunogenic than the standard hepatitis B vaccine regimen are needed in patients with human immunodeficiency virus 1 (HIV-1) infection.Objective To compare the safety and immunogenicity of 4 intramuscular double-dose and 4 intradermal low-dose regimens vs the standard hepatitis B vaccine regimen.Design, Setting, and Participants An open-label, multicenter, 1:1:1 parallel-group, randomized trial conducted between June 28, 2007, and October 23, 2008 (date of last patient visit, July 3, 2009) at 33 centers in France with patients enrolled in French National Agency for Research on AIDS and Viral Hepatitis trials in adults with HIV-1 infection who were hepatitis B virus (HBV) seronegative and having CD4 cell counts of more than 200 cells/mu L.Intervention Patients were randomly assigned to receive 3 intramuscular injections of the standard dose (20 mu g) of recombinant HBV vaccine at weeks 0, 4, and 24 (IM20 x 3 group, n=145); 4 intramuscular double doses (40 mu g [2 injections of 20 mu g]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (IM40 x 4 group, n=148); or 4 intradermal injections of low doses (4 mu g [1/5 of 20 mu g]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (ID4 x 4 group, n=144).Main Outcome Measures Percentage of responders at week 28, defined as patients with hepatitis B surface antibody (anti-HBs) of at least 10 mIU/mL in patients who received at least 1 dose of vaccine. Patients with missing anti-HBs titer measurement at the final follow-up visit at week 28 were considered as nonresponders in the primary (efficacy) analysis.Results A total of 437 patients were randomized to the 3 study groups, of whom 11 did not receive any vaccine. Of these, 396 had available anti-HBs titers at week 28. The percentage of responders at week 28 was 65% (95% confidence interval [CI], 56%-72%) in the IM20 x 3 group (n=91), 82% (95% CI, 77%-88%) in the IM40 x 4 group (n=119) (P < .001 vs IM20 x 3 group), and 77% (95% CI, 69%-84%) in the ID4 x 4 group (n=108) (P=.02 vs IM20 x 3 group). No safety signal and no effect on CD4 cell count or viral load were observed.Conclusion In adults with HIV-1, both the 4 intramuscular double-dose regimen and the 4 intradermal low-dose regimen improved serological response compared with the standard HBV vaccine regimen.