Antiviral prophylaxis to prevent perinatal transmission of HBV in Thailand

泰国抗病毒预防措施预防围产期乙型肝炎病毒传播

• 批准号: 9303744
• 负责人: Gonzague Joseph Jourdain
• 金额: $ 10万
• 依托单位: INSTITUTE OF RESEARCH AND DEVELOPMENT
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303744
• 关键词: Active Immunization; Acute; Adult; Alanine Transaminase; American; Antigens; Antiviral Agents; Antiviral Therapy; Asia; Asians; Birth; Cancer Etiology; Cause of Death; Cessation of life; Child; Childhood; Chronic; Chronic Hepatitis B; Cirrhosis; Country; Detection; Disease; Double-Blind Method; Effectiveness; Enrollment; Epidemic; European; Flare; Fumarates; Goals; Guidelines; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Transmission; Hepatitis B Vaccination; Hepatitis B Vaccines; Hepatitis B Virus; Hepatitis B e Antigens; High Risk Woman; Immune; Immunization Programs; Immunoglobulins; Infant; Infection; Institute of Medicine (U.S.); Intervention; Lamivudine; Letters; Life; Liver; Liver Function Tests; Liver diseases; Malignant neoplasm of liver; Mother-to-child HIV transmission; Mothers; Neonatal; Outcome; Passive Immunization; Perinatal; Perinatal Exposure; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Policies; Postpartum Period; Practice Guidelines; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention trial; Primary carcinoma of the liver cells; Prophylactic treatment; Public Health; Randomized; Randomized Clinical Trials; Recommendation; Risk; Risk Assessment; Safety; Site; Societies; Surface Antigens; Tenofovir; Testing; Thailand; Third Pregnancy Trimester; United States National Institutes of Health; Vaccination; Vertical Disease Transmission; Viral Load result; Virus; Virus Diseases; Virus Replication; Woman; anti-hepatitis B; comparative efficacy; discontinuation study; experience; immunoprophylaxis; improved; in utero; intrapartum; liver injury; passive immunoprophylaxis; prevent; transmission process; viral DNA; viral transmission

DESCRIPTION (provided by applicant): The proposed study is a phase III, multicenter, controlled, double blind, randomized clinical trial in Thailand to compare the efficacy, safety and tolerance of each of two drugs, tenofovir and lamivudine, versus placebo, given to hepatitis B (HB) chronically infected pregnant women with a positive HBeAg test and normal liver function tests, from 28 weeks' gestation until two months postpartum to prevent perinatal transmission of hepatitis B virus (HBV). Chronic HBV, complicated by cirrhosis and hepatocellular carcinoma (HCC), is the 10th leading cause of death worldwide. About 7% of Thai adults are HBsAg carriers. Universal immunization programs have dramatically reduced the prevalence of infection wherever they have been implemented. Infant HBV immunization and HB immunoglobulin administered at birth effectively prevent most transmission from HBV infected mothers but, despite this active and passive immunization, about 12% of HBV highly viremic mothers transmit the virus to their infants. The antigen HBe (HBeAg) is a marker of high replication. Studies have suggested that antiviral treatment at the end of pregnancy and in the postpartum can reduce the risk of transmission to the child. A potential limitation to this approach is the risk of hepatic disease exacerbation (flare) following discontinuation of antiviral treatment, which has not been properly evaluated. No randomized clinical trials have adequately demonstrated the efficacy and safety of antiviral treatment and this approach is not recommended by the Associations for the Study of Liver Diseases. We hypothesize that tenofovir or lamivudine can decrease HBV viral load in HBV infected pregnant women and therefore the risk of in utero, intrapartum and postpartum transmission before infants are protected by passive-active immunization. We also hypothesize that only moderate flares will be observed after discontinuation of a short antiviral course (5 months). While the primary objective of the study is to assess the efficacy of tenofovir or lamivudine versus placebo for the prevention of perinatal transmission, an important secondary objective is the assessment of the risk of postpartum hepatic disease exacerbation. HBsAg positive women will be enrolled if they have an HBeAg positive test and ALT 30 U/L. They will be randomized to receive tenofovir or lamivudine or placebo from 28 weeks of pregnancy until 2 months postpartum. Within 2 years, 588 women and their infants will be enrolled in 8 sites of the PHPT network in Thailand, where the teams have gained considerable experience in conducting trials for the prevention of mother to child transmission of HIV over the past 15 years. Mothers and infants will be followed until one year postpartum. The primary endpoint will be the detection of HBsAg and HBV DNA at six months of life. An interim analysis will be conducted when half of the outcomes are available. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.

描述（由申请人提供）：拟议的研究是一项在泰国进行的III期、多中心、对照、双盲、随机临床试验，以比较两种药物的疗效、安全性和安全性

项目成果

Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy.

• DOI: 10.1002/jcph.1746
• 发表时间: 2021-03
• 期刊: Journal of clinical pharmacology
• 影响因子: 2.9
• 作者: Bukkems VE;Smolders EJ;Jourdain G;Burger DM;Colbers AP;Cressey TR;PANNA Network and iTAP Study Group
• 通讯作者: PANNA Network and iTAP Study Group

Proximal tubular dysfunction in pregnant women receiving tenofovir disoproxil fumarate to prevent mother-to-child transmission of hepatitis B virus.

接受富马酸替诺福韦酯预防乙型肝炎病毒母婴传播的孕妇的近端肾小管功能障碍。

• DOI: 10.1093/jac/dkab490
• 发表时间: 2022
• 期刊: The Journal of antimicrobial chemotherapy
• 作者: Liegeon,Geoffroy;Ngo-Giang-Huong,Nicole;Salvadori,Nicolas;Bunpo,Piyawan;Cressey,Ratchada;Achalapong,Jullapong;Kanjanavikai,Prateep;PatamasinghNaAyudhaya,Orada;Prommas,Sinart;Siriwachirachai,Thitiporn;Sabsanong,Prapan;YvesMary,Jea
• 通讯作者: YvesMary,Jea