Prevention of Maternal-to-Infant HIV Transmission/India

此竞争性续展(类型2)申请的目标是申请额外资金，以 在印度浦那完成一项由美国国立卫生研究院赞助的名为“预防母婴传播”的第三阶段临床试验。 2002年8月16日发起的《印度的婴儿艾滋病毒传播》。这项研究是一项随机、双臂、 对感染艾滋病毒的母亲及其母乳喂养的婴儿进行开放标记试验，以比较其安全性 标准母婴单剂奈韦拉平(ARM 1)对单剂NVP的疗效 产后6周的方案加婴儿每日小剂量NVP(第2组)。这项试验的主要结果是 产后6个月婴儿HIV感染率比较这项研究也有二次 目标，包括产后9个月母体NVP耐药性的测定，以及 对参与研究的母亲及其婴儿的死亡率和发病率的测量。在16岁之间 2002年8月和2004年7月31日，20,800多名母亲接受了艾滋病毒筛查，408人 符合条件的母亲已经参加了临床试验。此类型2建议书最初是为 回顾9月1日2003年12月30日修订并重新提交，现已第三次修订以解决 关于应计和留存的最近一次审查的主要关切。自上次提交此文件以来 在这项提议中，已经发生了两个关键变化，这将极大地促进这一试验的成功完成。第一, 自8月以来，我们在印度的试用注册率从平均每周3人增加了一倍多 32岁和2003年12月，自2004年1月以来，平均每周6次。其次，在2004年2月，NIAID 用于该临床试验的DSMB建议将来自印度的该试验的主要终点数据与 来自埃塞俄比亚和乌干达类似试验点的数据。这一建议得到了一致性的推动 N试验设计、研究干预、资格标准、数据管理程序和研究程序 所有三个地点。新合并分析的总样本量为1964，其中将包括730的数据 来自我们在印度的试验点的孩子。修订后的分析计划也大大缩短了时间(从3年减少到2年) 以及这项提案的成本(现在是我们上一次拨款申请所要求成本的44.2%)。在我们的 按照目前的应计比率，我们预计到2005年7月底，印度将达到730个的新目标。

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 procedures for 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.