Standard zidovudine plus infant nevirapine to prevent perinatal HIV in Thailand

标准齐多夫定加婴儿奈韦拉平预防泰国围产期艾滋病毒

• 批准号: 7498440
• 负责人: MARC J LALLEMANT
• 金额: $ 73.36万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-29 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498440
• 关键词: AIDS prevention; Anti-Retroviral Agents; Birth; Botswana; CD4 Lymphocyte Count; Cesarean section; Child; Clinical; Collaborations; Consent; Delivery Rooms; Developed Countries; Developing Countries; Dose; Double-Blind Method; Drug Kinetics; End Point; Enrollment; Evaluable Disease; France; Future; Guidelines; HIV; HIV-1; Health; Highly Active Antiretroviral Therapy; Hospitals; Hour; Immune; Immunocompromised Host; Infant; Knowledge; Labor Onset; Lamivudine; Lamivudine/Zidovudine; Mothers; Mutation; Nevirapine; Oral; Patient currently pregnant; Perinatal; Pharmaceutical Preparations; Phase; Placebo Control; Policies; Postpartum Period; Pregnancy; Pregnant Women; Prevention; Prevention Guidelines; Prevention program; Prevention strategy; Preventive Intervention; Prophylactic treatment; Public Health; Public Hospitals; Randomized; Rate; Recommendation; Research; Research Personnel; Resistance; Resources; Risk; Role; Safety; Sample Size; Schedule; Specimen; Standards of Weights and Measures; Testing; Thailand; Therapeutic; Treatment Protocols; Universities; Upper arm; Viral; Week; Woman; World Health Organization; Zidovudine; antiretroviral therapy; base; clinical research site; cost; day; feeding; intrapartum; neonate; nevirapine resistance; non-nucleoside reverse transcriptase inhibitors; prevent; programs; transmission process

DESCRIPTION (provided by applicant): The 2nd Perinatal HIV Prevention Trial (PHPT-2) in Thailand showed that a single dose of nevirapine (SD- NVP) to women at onset of labor and to infants at 48-72 hours in addition to zidovudine (ZDV) starting at 28 weeks' gestation, could reduce HIV perinatal transmission to about 2%. However, post-exposure NVP resistance mutations detected in mothers have raised concerns regarding future efficacy of Non Nucleoside Reverse Transcriptase Inhibitor based treatments for their own health. Results from a study in Botswana suggested that maternal SD-NVP may not be needed if the infant SD-NVP is administered immediately after birth. The study primary objective is to test whether maternal SD-NVP can be omitted without loss of efficacy in preventing perinatal HIV transmission. A regimen with no maternal NVP and two infant NVP doses, one immediately after birth, the other after 48-72 hours, will be compared for efficacy with a regimen including a maternal NVP dose during labor and identical infant NVP dosing. ZDV prophylaxis will be provided from 28 weeks gestation or as soon as possible thereafter, loading dose during labor and 1 week in the infants. All infants will be formula fed. To diminish the risk of selecting NVP resistance mutations, mothers exposed to NVP will receive a one week course of ZDV plus lamivudine, following WHO and Thai guidelines. The secondary objectives are to study HIV resistance mutations to NVP in HIV infected infants, to compare the safety of both strategies in mothers and infants and to study the pharmacokinetics of NVP in infants. This multicenter, phase III, randomized, double-blind, controlled trial will enroll 1398 consenting HIV-1 infected pregnant women, with CD4 count >200/mm3, participating in the Thai Ministry of Public Health (MoPH) prevention program, assigned to one of the 2 study arms (699 per arm including 5% non evaluable; power: 80%; delta threshold for non-inferiority testing between groups: 1.5%). The primary endpoint is infant HIV status based on confirmed DNA-PCR results on specimens drawn at birth, 1, 2, 4 and 6 months. The study will build upon PHPT-1 and PHPT-2, a collaborative effort between Harvard University, IRD- France, the Thai MoPH, and Mahidol and Chiang Mai Universities, through a network of 39 public hospitals. If maternal NVP proves unnecessary, a simple regimen will be available for the prevention of perinatal HIV transmission, resistance mutations avoided, and maternal future drug options preserved. This study will have important public health implications in settings where NVP, with or without ZDV background, is a central component of the prevention of intrapartum transmission, It will also provide key scientific knowledge on the role of post-exposure prophylaxis in the prevention of intrapartum HIV transmission.

描述（由申请方提供）：泰国第二次围产期HIV预防试验（PHPT-2）显示，从妊娠28周开始，除齐多夫定（ZDV）外，在分娩开始时对妇女和48-72小时的婴儿单剂量奈韦拉平（SD-NVP）可将HIV围产期传播降低至约2%。然而，在母亲中检测到的暴露后NVP抗性突变引起了对基于非核苷逆转录酶抑制剂的治疗对其自身健康的未来疗效的担忧。博茨瓦纳的一项研究结果表明，如果婴儿出生后立即给予SD-NVP，则可能不需要母体SD-NVP。该研究的主要目的是测试是否可以省略母体SD-NVP而不丧失预防围产期HIV传播的功效。将比较无母体NVP和两次婴儿NVP给药（一次在出生后立即给药，另一次在48-72小时后给药）的方案与包括分娩期间母体NVP给药和相同婴儿NVP给药的方案的疗效。从妊娠28周开始或此后尽快提供ZDV预防，分娩期间和婴儿1周时给予负荷剂量。所有的婴儿都将由配方奶粉喂养。为了减少选择性NVP耐药突变的风险，暴露于NVP的母亲将按照WHO和泰国指南接受为期一周的ZDV加拉米夫定治疗。次要目的是研究HIV感染婴儿对NVP的HIV耐药突变，比较两种策略在母亲和婴儿中的安全性，并研究NVP在婴儿中的药代动力学。这项多中心、III期、随机、双盲、对照试验将招募1398名同意的HIV-1感染孕妇，CD 4计数>200/mm 3，参加泰国公共卫生部（MoPH）预防计划，分配到2个研究组之一（每组699例，包括5%不可评价;把握度：80%;组间非劣效性检验的δ阈值：1.5%）。主要终点是基于出生、1、2、4和6个月时采集的样本的经确认的DNA-PCR结果的婴儿HIV状态。该研究将建立在PHPT-1和PHPT-2的基础上，这是哈佛大学、IRD-法国、泰国公共卫生部、玛希隆大学和清迈大学通过39家公立医院网络进行的合作。如果产妇NVP被证明是不必要的，一个简单的方案将可用于预防围产期艾滋病毒传播，避免耐药突变，并保留产妇未来的药物选择。本研究将在NVP（有或无ZDV背景）是预防分娩期传播的核心组成部分的环境中具有重要的公共卫生意义，还将提供有关暴露后预防在预防分娩期HIV传播中的作用的关键科学知识。