Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Research Institutes for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
AIDS Res Ther. 2019 Nov 11;16(1):33. doi: 10.1186/s12981-019-0249-8.
We previously reported that four doses or four double doses of hepatitis B vaccination regimens could not significantly increase a response rate compared with standard doses. However, the antibody levels were higher in the four doses and four double doses groups. This study followed those patients for at least 3 years and aimed to evaluate the immunogenicity of the three vaccination regimens.
HIV-infected adults who had CD4+ cell counts > 200 cells/mm, undetectable plasma HIV-1 RNA, and negative for all hepatitis B virus markers were randomly assigned to receive one of three recombinant vaccines (Hepavax-Gene Berna, Korea) regimens: 20 μg IM at months 0, 1, and 6 (standard doses group, n = 44), 20 μg IM at months 0, 1, 2, 6 (four doses group, n = 44), or 40 μg IM at months 0, 1, 2, and 6 (four double doses group, n = 44) between February 2011 and May 4, 2012. Of 132 participants, 126 were evaluated from August 2015 to January 2016; 42 in the standard doses, 43 in the four doses, and 41 in the four double doses groups.
At a median duration of 49.7 months (range 46.7-53.7) after completion of the primary vaccination schedule, the percentages of responders with anti-HBs ≥ 10 mIU/mL were 57.1% (95% CI 41.5-72.8%) in the standard doses group; 76.7% (95% CI 63.6-89.9%) in the four doses group (P = 0.067 vs. the standard doses group); and 80.5% (95% CI 67.8-93.2%) in the four double doses group (P = 0.033 vs. the standard doses group). Factors associated with a responder were the vaccination schedule (either four doses or four double doses groups) and a younger age.
Despite the highly effectiveness of the standard hepatitis B vaccination regimen at 6 months after completion, the long-term immunogenicity was lower than the four double doses regimen among HIV-infected adults with CD4+ cell counts > 200 cells/mm and undetectable plasma HIV-1 RNA. The standard vaccination regimen may not be the best strategy to provide long-term immune response against hepatitis B virus among HIV-infected individuals. Trial registration NCT1289106, NCT02713620.
我们之前报道过，与标准剂量相比，乙肝疫苗接种四剂或四剂加倍剂量并不能显著提高应答率。然而，四剂和四剂加倍剂量组的抗体水平更高。本研究对这些患者进行了至少 3 年的随访，旨在评估三种疫苗接种方案的免疫原性。
HIV 感染的成年人 CD4+细胞计数>200 个/毫米 3 、血浆 HIV-1 RNA 未检出且所有乙型肝炎病毒标志物均为阴性，被随机分配至接受三种重组疫苗（韩国 Hepavax-Gene Berna）方案之一：0、1 和 6 个月时肌内注射 20μg（标准剂量组，n=44）、0、1、2 和 6 个月时肌内注射 20μg（四剂组，n=44）或 0、1、2 和 6 个月时肌内注射 40μg（四剂加倍剂量组，n=44），时间为 2011 年 2 月至 2012 年 5 月 4 日。在 132 名参与者中，有 126 名于 2015 年 8 月至 2016 年 1 月进行了评估；标准剂量组 42 名，四剂组 43 名，四剂加倍剂量组 41 名。
在原发性疫苗接种方案完成后中位数 49.7 个月（范围 46.7-53.7）时，抗-HBs≥10mIU/mL 的应答者百分比为标准剂量组 57.1%（95%CI 41.5-72.8%）；四剂组 76.7%（95%CI 63.6-89.9%）（与标准剂量组相比，P=0.067）；四剂加倍剂量组 80.5%（95%CI 67.8-93.2%）（与标准剂量组相比，P=0.033）。与应答者相关的因素是疫苗接种方案（四剂或四剂加倍剂量组）和年龄较小。
尽管标准乙肝疫苗接种方案在完成后 6 个月时具有高度有效性，但在 CD4+细胞计数>200 个/毫米 3 且血浆 HIV-1 RNA 未检出的 HIV 感染成年人中，长期免疫原性低于四剂加倍剂量方案。标准疫苗接种方案可能不是为 HIV 感染者提供针对乙型肝炎病毒长期免疫应答的最佳策略。试验注册 NCT1289106、NCT02713620。
