Antiviral prophylaxis and infant vaccination to prevent perinatal hepatitis B infection

抗病毒预防和婴儿疫苗接种以预防围产期乙型肝炎感染

• 批准号: 10490246
• 负责人: Gonzague Joseph Jourdain
• 金额: $ 40.92万
• 依托单位: INSTITUTE OF RESEARCH AND DEVELOPMENT
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490246
• 关键词: Active Immunization; Address; Adult; Adverse event; Age-Months; Antibodies; Antibody Response; Antigens; Antiviral Agents; Birth; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Chronic Hepatitis B; Cirrhosis; Clinical Research; Clinical Trials; Congenital Abnormality; Data; Detection; Dose; Double-Blind Method; Enrollment; Fetus; Fumarates; Guidelines; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Infection; Hepatitis B Surface Antigens; Hepatitis B Transmission; Hepatitis B Vaccination; Hepatitis B Vaccines; Hepatitis B Virus; Immunoglobulins; Infant; Infection; Infection prevention; Laos; Life; Malignant neoplasm of liver; Maternal-Fetal Transmission; Mothers; National Institute of Child Health and Human Development; Newborn Infant; Perinatal; Perinatal transmission; Persons; Phase; Placebo Control; Placebos; Policies; Population; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnant Women; Prevention; Program Efficiency; Prophylactic treatment; Protocols documentation; Public Health; Publishing; Randomized; Randomized Clinical Trials; Reporting; Resource-limited setting; Risk; Risk Estimate; Safety; Site; Surface Antigens; Telbivudine; Tenofovir; Testing; Thailand; Third Pregnancy Trimester; Vaccinated; Vaccination; Vaccines; Vertical Disease Transmission; Viral; Viral Load result; Viremia; Virus; Virus Diseases; Virus Replication; Woman; anti-hepatitis B; arm; chronic infection; high risk; improved; in utero; infant infection; infant outcome; infection risk; innovation; intrapartum; liver injury; maternal safety; open label; particle; postnatal period; pre-exposure prophylaxis; prevent; primary endpoint; prospective; response; transmission process; viral DNA; viral transmission; virtual

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.

项目摘要 绝大多数围产期肝炎B（HB）感染成为慢性感染，引起肝硬化和肝脏 成年后的癌症。超过2.5亿人（占全球人口的6％）被长期感染 HB病毒（HBV），每年造成近780,000人死亡。通用HB免疫，从出生开始 疫苗的剂量不足以防止所有母亲到孩子的传播，尤其是当母亲高的时候 病毒载荷。在这种情况下，除疫苗外，还建议使用HB免疫球蛋白（HBIG）。 在三项研究中，包括我们小组在泰国进行的随机临床试验（ITAP），没有传输 当母亲在怀孕结束时和产后早期接受抗HBV抗病毒药物治疗时发生 时期。孕产妇抗病毒治疗将病毒载量降低到很少传播的母亲中看到的水平 病毒。在这些研究中，母亲和婴儿的抗病毒治疗是安全且容忍的。 我们假设HBIG可以用出生时接种疫苗的婴儿的母体抗病毒治疗代替。 我们的主要目的是证明，当接受抗病毒预防的高病毒血症的母亲 当新生儿没有收到HBIG时，向婴儿传播HBV的风险小于2％，最低 没有抗病毒的传输速率。 鉴于HBIG并非广泛可用，并且大多数受HBV感染的婴儿，这与公共卫生有关 母亲没有收到它，而HBIG加上出生时施用的疫苗不能阻止所有感染，尤其是 那些已经在子宫内建立的。这种创新策略从未在经过精心控制的环境中进行测试。 我们建议对患有高母亲 从28-30周开始接受抗病毒替诺福韦的抗病毒替诺福（TDF）的病毒血症（HBE抗原阳性） 妊娠到产后2个月，而婴儿接受主动免疫接种，但没有HBIG。该研究将是 在泰国和老挝PDR进行，将在我们临床的32个地点注册439名妇女及其婴儿 研究网络。 HBSAG阳性女性如果有HBEAG阳性测试（广泛可用的） 高病毒复制测试）。母亲将被遵循，直到产后一年和婴儿18个月。这 主要终点将是通过PCR在六个月生命时检测到HBV DNA确认的HBSAG的检测。 证明抗病毒治疗加疫苗足以防止几乎所有围产期HBV 不使用HBIG的传输将彻底改变HBV PMTCT。研究结果将有助于定义 通过HBEAG阳性测试管理HBV感染孕妇的政策，以防止围产期传播。