NEVIRAPINE+ZIDOVUDINE--PREVENT PERINATAL HIV IN THAILAND

齐多夫定（ZDV）预防妊娠期高血压疾病的疗效观察 ACTG 076确定的艾滋病毒母婴传播已得到证实 在所有的后续研究中，在所有的设置。尽管使用了ZDV预防 和母乳喂养，重大的艾滋病毒传播仍然发生在子宫内， 在分娩过程中。接受ZDV的妇女计划剖腹产已被证明， 几乎消除了分娩期间的传播，但其使用可能与 发病率和费用增加，特别是在发展中国家。使用 在分娩和分娩期间额外的抗逆转录病毒药物可以是一种替代方案， 奈韦拉平（NVP），一种有效的抗逆转录病毒药物，可能是首选药物。当 在分娩期间给予母亲单次NVP剂量， 出生后30天，分娩期和产后早期感染的风险为 在最近的一项非洲研究中， 婴儿。拟议研究的主要目的是评估疗效， 临产时单次给予NVP的安全性和耐受性 以及出生后48至72小时的婴儿，除了目前的泰国人， ZDV预防团。次要目标是研究各自的 探讨母婴NVP的作用，进一步探讨NVP的病理生理机制， 和艾滋病毒垂直传播的时间以及研究传播的辅助因素 （临床状态、足月分娩方式、病毒载量、表型和辅助受体 用途;宿主遗传学和细胞免疫应答;以及NVP和ZDV 抗性相关突变）。为了实现这些目标，我们提出了一个阶段 III期、双盲、随机、安慰剂对照试验，给予200 mg NVP， 分娩开始时的妇女和出生后48至72小时的婴儿2毫克/公斤， 除了目前的Thai ZDV方案（ZDV从34周开始， 胎龄、持续分娩和分娩以及婴儿1周 ZDV）。研究人群将是同意的HIV-1感染孕妇 参加Tahi MOPH ZDV预防计划和非母乳喂养的 新生儿，1，530名女性将随机分配至3个研究组之一： NVP/母亲-NVP/婴儿或安慰剂/母亲-安慰剂/婴儿组用于主要研究 比较;或NVP/母亲-安慰剂/婴儿，一个中间组，将提供 关于治疗的相对重要性的额外信息 母亲和婴儿在HIV-1传播中的治疗。的 主要终点是婴儿HIV状态，基于经确认的DNA-PCR结果， 在出生、6周、4个月和6个月时抽取样本。该研究将建立 泰国围产期艾滋病毒预防试验（PHPT）， 哈佛大学、法国IRD、法国公共卫生部 泰王国、玛希隆大学和清迈大学， 已在27家医院建立了临床医生团队、资源和网络 泰国全境（主要在曼谷、东部和北方省份 泰国）。

The efficacy of zidovudine (ZDV) for the prevention of mother-to-child transmission of HIV established by ACTG 076 has been confirmed in all subsequent studies in all settings. Despite the use of ZDV prophylaxis and breastfeeding, significant HIV transmission still occurs in utero and during delivery. Planned c-section in women receiving ZDV has been shown to nearly eliminate intrapartum transmission, but its use may be associated with increased morbidity and cost, especially in developing countries. The use of additional antiretrovirals during labor and delivery could be an alternative, and nevirapine (NVP), a potent antiretroviral, may be the drug of choice. When a single NVP dose was given to the mother during labor and to the infants 3 days after birth, the risk of intrapartum and early postnatal infection was dramatically reduce in a recent African study where women breastfed their infants. The primary objective of the proposed study is to assess the efficacy, safety and tolerance of a single dose of NVP given to women at onset of labor and to their infant 48 to 72 hours after birth, in addition to the current Thai ZDV prophylaxis regiment. Secondary objectives are to study the respective roles of the maternal and the infant NVP, further explore the physiopathology and timing of vertical HIV transmission and study co-factors of transmission (clinical status, term mode of delivery; viral load, phenotype and coreceptor use; host genetics and cellular immune response; and NVP and ZDV resistance-related mutations). To meet these objectives, we propose a phase III, double-blind, randomized, placebo controlled trial of 200mg NVP given to women at onset of labor and 2mg/kg to the infant 48 to 72 hours after birth, in addition to the current Thai ZDV regimen (ZDV starting at 34 weeks of gestational age, continuing through labor and delivery, and 1 week of infant ZDV). The study population will be consenting HIV-1 infected pregnant women enrolled in the Tahi MOPH ZDV prevention program and their non-breastfed newborns, 1,530 women will be randomized in one of 3 study arms: NVP/mother-NVP/infant or Placebo/mother-Placebo/infant arms for the primary comparison; or NVP/mother-Placebo/infant, an intermediate arm that will provide additional information as to the relative importance of the treatment of the mother and the treatment of the infant in the transmission of HIV-1. The primary endpoint is infant HIV status based on confirmed DNA-PCR results on specimens drawn at birth, 6 weeks, 4 months and 6 months. The study will build on the Perinatal HIV Prevention Trial (PHPT) in Thailand, a collaborative effort between Harvard University, IRD-France, the Ministry of Public Health of Kingdom of Thailand, and Mahidol and Chiang Mai Universities, using the study team, resources and network of clinicians already established in 27 hospitals throughout Thailand (mainly in Bangkok and the eastern and northern provinces of Thailand).