Birth Outcomes Surveillance in Botswana

描述(由申请人提供)：世界卫生组织指南推荐Atripla(Efavirenz(EFV)/恩曲他滨(FTC)/替诺福韦(TDF))用于抗逆转录病毒治疗(ART)，包括在怀孕的所有三个月期间。由于对早期灵长类数据和有限的人类报告中EFV所致神经管缺陷(NTDS)的担忧，到目前为止，在怀孕前三个月使用EFV的情况很少，而且几乎没有数据可以保证目前世卫组织的建议不会对NTDS构成小幅增加的风险。此外，有关Atripla对早产、小于胎龄儿、先天性畸形、死产和新生儿死亡等其他分娩结果的影响的数据有限。因此，我们计划建立一个全国性的监测系统，以捕获博茨瓦纳50%的新生儿，并研究Atripla对不良生育结局和NTDS发生率的影响。博茨瓦纳最近修改了国家指南，允许将Atripla用于治疗和预防艾滋病毒感染妇女中艾滋病毒的母婴传播。这一指南的变化使我们能够掌握Atripla的推出时间，并比较EFV暴露和其他ART方案暴露从受孕开始的结果。在进行监测的过程中，我们还将在感染艾滋病毒和未感染艾滋病毒的妇女所生婴儿中建立NTDS和其他临床上重要的先天性异常的基线比率。博茨瓦纳是建立这种监测的理想环境，因为从受孕开始就有大量的抗逆转录病毒药物暴露(我们预计全球范围内记录的EFV暴露结果数量的三倍以上)，在产科病房分娩的妇女比例很高，以及之前对全国超过33,000名新生儿进行的成功监测研究。这项研究的综合目的将提供对在妊娠期使用Atripla与其他ART方案相比的风险的全面了解。

DESCRIPTION (provided by applicant): World Health Organization guidelines recommend Atripla (Efavirenz (EFV) / Emtricitabine (FTC) / Tenofovir (TDF)) for antiretroviral treatment (ART), including during all trimesters of pregnancy. Because of concerns for neural tube defects (NTDs) with EFV from early primate data and from limited human reports, EFV use in the first trimester of pregnancy has been rare to date, and few data exist to provide reassurance that the current WHO recommendations do not pose a small increased risk for NTDs. In addition, limited data are available regarding the effect of Atripla on other birth outcomes such as preterm delivery, small for gestational age infants, congenital abnormalities, stillbirths, and neonatal deaths. We therefore plan to create a nationwide surveillance system to capture 50% of births that occur in Botswana, and to study the effect of Atripla on adverse birth outcomes and on the rate of NTDs. National guidelines in Botswana have recently changed to allow Atripla use for both treatment and for the prevention of mother- to-child HIV transmission among HIV-infected women. This guideline change allows us to capture the rollout period for Atripla, and to compare outcomes for both EFV exposures and other ART regimen exposures from conception. In the process of performing this surveillance, we will also establish baseline rates of NTDs and other clinically important congenital abnormalities among infants born to HIV-infected and HIV-uninfected women. Botswana is an ideal setting to establish this surveillance because of the large number of ART exposures from conception (we expect to more than triple the current number of documented outcomes with EFV exposure worldwide), the high percentage of women delivering at maternity wards, and a successful previous surveillance study of over 33,000 births throughout the country. The combined aims of this study will provide a comprehensive understanding of the risks of using Atripla compared with other ART regimens during pregnancy.