Prevention of Maternal-to-Infant HIV Transmission/India

此竞争性延续（类型2）申请的目的是申请额外资金， 在印度浦那完成了一项正在进行的NIH赞助的III期临床试验，题为“预防母婴传播”， 印度的婴儿艾滋病毒传播情况”，2002年8月16日发起。本研究是一项随机、2组、 一项在HIV感染母亲及其母乳喂养婴儿中进行的开放标签试验，旨在比较 标准母体/婴儿奈韦拉平（NVP）单次给药（第1组）与NVP单次给药的疗效 方案加低剂量每日婴儿NVP，产后6周（组2）。这项试验的主要结果是 产后6个月婴儿艾滋病毒感染率的比较。这项研究也有次要的 目的，包括测量产后9个月的母体NVP耐药性，以及 测量参与的母亲及其婴儿的死亡率和发病率。16岁以下 2002年8月和2004年7月31日，20 800多名同意的母亲接受了艾滋病毒筛查，408名母亲接受了艾滋病毒筛查。 符合条件的母亲已参加临床试验。这一类型2提案最初提交给 回顾9月1日2003年，2003年12月30日修订并重新提交，现已第三次修订， 最近一次审查对应计和留存的主要关切。自从上次提交这份 根据提议，发生了两个关键变化，这将极大地促进本试验的成功完成。第一、 我们在印度的试验入组率从8月到12月， 自2004年1月以来，每周平均6次。第二，2004年2月，NIAID 本临床试验的DSMB建议合并印度试验的主要终点数据， 来自埃塞俄比亚和乌干达类似试验地点的数据。这一建议是由一致性促进的， 试验设计、研究干预、合格标准、数据管理程序和研究程序 三个网站。这个新的合并分析的总样本量是1964，其中包括730 我们在印度试验基地的婴儿。修订后的分析计划也大大缩短了时间（从3年缩短到2年） 以及这项提案的成本（现在是我们上次提交赠款时要求的成本的44.2%）。在我们 根据目前的应计比率，我们预计到2005年7月底在印度达到730个新目标。

The objective of this Competitive Continuation (Type 2) application is to request additional funding to complete an ongoing NIH-sponsored Phase III clinical trial in Pune, India entitled "Prevention of Mother-to- Infant HIV Transmission in India", which was initiated 16August 2002. This study is a randomized, 2-arm, open-labeled trial among HIV-infected mothers and their breast-fed infants designed to compare the safety and efficacy of standard maternal/infant single dose nevirapine (NVP) (Arm 1) to the single dose NVP regimen plus low-dose daily infant NVP for 6 weeks post-partum (Arm 2). The primary outcome of this trial is the comparison of infant HIV infection rates at 6 months post-partum. This study also has secondary objectives, including the measurement of maternal NVP drug resistance at 9 months postpartum, as well as the measurement of mortality and morbidity rates among participating mothers and their infants. Between16 August 2002 and 31 July 2004, more than 20,800 consenting mothers have been HIV screened and 408 eligible mothers have been enrolled in the clinical trial. This Type 2 proposal was initially submitted for review 1 Sept. 2003, revised and re-submitted 30 Dec. 2003 and has now been revised a 3rd time toaddress the key concerns of the most recent review about accrual and retention. Since the last submission of this proposal, 2 key changes have occurred that will greatly facilitate the successful completion of this trial. First, our enrollment rate for the trial in India has more than doubled from an average of 3/week, between August 32 and December 03, to an average of 6/week, since January 2004. Secondly, in February 2004, the NIAID DSMB for this clinical trial recommended the merging of the primary endpoint data from this trial in India,with data from similar trial sites in Ethiopia and Uganda. This recommendation was facilitated by the consistency n trial designs, study interventions, eligibility criteria, data management procedures and study proceduresfor all three sites. The total sample size for this new merged analysis is 1964, which will include data from 730 nfants from our trial site in India. The revised analysis plan also greatly reduces the time (from 3 to 2 years) and the cost of this proposal (now 44.2% of the cost requested with our last grant submission). At our current accrual rate, we expect to reach our new target of 730 in India by the end of July 2005.