Antiviral prophylaxis and infant vaccination to prevent perinatal hepatitis B infection

项目摘要 绝大多数围产期B型肝炎（HB）感染会变成慢性感染，导致肝硬化和肝硬化。 成年期的癌症超过2.5亿人（约占世界人口的6%）是慢性感染者 乙肝病毒（HBV），每年造成近78万人死亡。从出生开始的全面乙肝免疫接种 但是，一剂疫苗不足以预防所有母婴传播，特别是当母亲患有高血压时， 病毒载量在这种情况下，除了疫苗外，还建议使用HB免疫球蛋白（HBIg）。 在三项研究中，包括我们在泰国进行的随机临床试验（iTAP）， 当母亲在妊娠末期和产后早期接受抗HBV抗病毒治疗时， 期母体抗病毒治疗可将病毒载量降至很少传播的母亲的水平 病毒在这些研究中，抗病毒治疗是安全的，母亲和婴儿耐受性良好。 我们假设HBIg可以被母亲抗病毒治疗所取代，用于出生时接种疫苗的婴儿。 我们的主要目的是证明，当接受抗病毒预防治疗的高病毒血症母亲 当新生儿未接受HBIg时，HBV传播给婴儿的风险低于2%，最低 在没有抗病毒药物的情况下， 这与公共卫生有关，因为HBIg并不广泛可用，大多数婴儿出生时都感染了HBV 母亲不接受它，出生时接种HBIg加疫苗不能预防所有感染，特别是 那些在子宫里就已经形成的这一创新策略从未在严格控制的环境中进行过测试。 我们提出了一项多中心、开放标签、单臂、前瞻性的临床研究，研究对象是高血压母亲所生的婴儿。 从28-30周开始接受抗病毒药物富马酸替诺福韦酯（TDF）治疗的病毒血症（HBe抗原阳性）患者 妊娠期至产后2个月，而婴儿接受主动免疫，但没有HBIg。本研究将 在泰国和老挝人民民主共和国进行，将在我们的临床试验的32个地点招募439名妇女及其婴儿。 研究网络。如果HBsAg阳性女性的HBeAg检测结果为阳性（广泛可用的 高病毒复制试验）。母亲将被跟踪到产后一年，婴儿18个月。的 主要终点将是6个月时通过PCR检测HBV DNA确认的HBsAg检测。 证明抗病毒治疗加疫苗足以预防几乎所有围产期HBV 不使用HBIg的HBV传播将彻底改变HBV PMTCT。研究结果将有助于确定 管理HBeAg阳性的HBV感染孕妇的政策，以防止围产期传播。

PROJECT SUMMARY The vast majority of perinatal hepatitis B (HB) infections become chronic infections, causing cirrhosis and liver cancer in adulthood. More than 250 million people (about 6% of the world's population) are chronically infected with HB virus (HBV), causing nearly 780,000 deaths each year. Universal HB immunization, starting with a birth dose of vaccine, is not sufficient to prevent all mother-to-child transmission, especially when mothers have high viral loads. In such cases, administration of HB immune globulin (HBIg) is recommended in addition to vaccine. In three studies, including a randomized clinical trial (iTAP) conducted by our group in Thailand, no transmissions occurred when mothers received an anti-HBV antiviral treatment at the end of pregnancy and early postpartum period. Maternal antiviral treatment decreases viral loads to those levels seen in mothers who seldom transmit the virus. In these studies, the antiviral treatment was safe and well tolerated by the mothers and infants. We hypothesize that HBIg can be replaced by maternal antiviral treatment for infants vaccinated at birth. Our primary objective is to demonstrate that, when mothers with high viremia who receive antiviral prophylaxis and when the newborn does not receive HBIg, the risk of HBV transmission to infants is less than 2%, the lowest rate of transmission ever reported without antiviral. This is relevant to public health given that HBIg is not widely available and most infants born to HBV infected mothers do not receive it and that HBIg plus vaccine administered at birth cannot prevent all infections, especially those already established in utero. This innovative strategy has never been tested in a carefully controlled setting. We propose a multicenter, open-label, single arm, prospective clinical study in infants born to mothers with high viremia (HBe antigen positive) who receive the antiviral tenofovir disoproxil fumarate (TDF) from 28-30 weeks gestation until 2 months postpartum, while infants receive active immunization but no HBIg. The study will be conducted in Thailand and Laos PDR and will enroll 439 women and their infants in 32 sites of our clinical research network. HBsAg positive women will be enrolled if they have an HBeAg positive test (a widely available test of high virus replication). Mothers will be followed until one year postpartum and infants 18 months. The primary endpoint will be the detection of HBsAg confirmed by PCR detection of HBV DNA at six months of life. Demonstrating that antiviral treatment plus vaccine is sufficient to prevent virtually all perinatal HBV transmissions without the use of HBIg would revolutionize HBV PMTCT. The results of the study will help define policy to manage HBV infected pregnant women with an HBeAg positive test to prevent perinatal transmission.