Feasibility and Cost of WHO PMTCT Option A vs. B in Rural and Urban Uganda

摘要 在乌干达和其他撒哈拉以南非洲国家一样，卫生部正在进行 通过和实施世卫组织2010年防止母婴传播新指南。这些指导方针 建议对以下孕妇使用两种ARV预防方案中的一种 不需要为了自己的健康而接受抗逆转录病毒治疗(ART)。备选方案A由孕产妇组成 AZT在整个妊娠和分娩过程中进行预防，并辅以每日奈韦拉平治疗 婴儿从出生到完全停止母乳喂养一周后。备选方案B包括 孕期14周至完全停药后一周的三联疗法 在母乳喂养的基础上，婴儿每日服用奈韦拉平，为期六周。这两个选项 显著降低艾滋病毒母婴传播的风险，但他们的 在操作可行性、安全性和可接受性方面的优势和劣势 因为成本尚未评估。世界卫生组织的指导方针规定：“首选的 应在国家一级作出选择，在考虑到这些优势和 目前缺乏支持这一决定所需的证据，这是至关重要的 对于像乌干达这样试图做出明智选择的国家来说，这是必要的 在全国范围内推广。 此运筹性研究提案的总体目标是比较交付 年，世卫组织在坎帕拉两家城市医院和两家乡村医院预防母婴传播备选方案A和B。 乌干达。我们将招募600名符合条件的(CD4&>350)艾滋病毒感染孕妇参加这两个项目 选项A或B，总共有1,200对母婴进入研究。在每个城市或农村地区， 一家医院将被分配到选项A，另一家将被分配到选项B。在每家医院，300项研究 参与者将被登记并在产后随访12个月。的主要目标是 这项研究将比较备选方案A和B在以下方面的执行情况：1)产妇 和婴儿PMTCT药物依从性的自我报告、药片计数和ARV药物检测 目的2)母体药物相关的严重不良事件和妊娠结局；以及 婴儿安全；目标3)任一选项的成本效益。 这项研究将被用来检测10%或更多的药物依从性差异 在防止母婴传播服务级联中的四个关键时间点累积，包括第三个 与免疫接种和婴儿早期艾滋病毒相对应的三个月和三次产后访问 诊断计划：分娩后6周、6个月和12个月或在分娩时 停止母乳喂养。次要终端将包括艾滋病毒垂直传播率 根据婴儿出生时、6周、6个月和12岁时血液中艾滋病毒DNA的存在情况 婴儿的12个月无艾滋病毒存活和暴露于艾滋病毒的婴儿的总存活率； 以及产后12个月随访期内再次怀孕的发生率。我们 将利用焦点小组讨论和主要线人访谈来评估 在感染艾滋病毒的母亲、服务提供者和社区卫生中选择预防母婴传播方案 领袖们。这项研究的结果将为业务决策提供关键证据 关于当前世卫组织防止母婴传播建议在以下背景下的可行性 资源受限设置。

ABSTRACT In Uganda as in other sub-Saharan African countries, the Ministry of Health is in the process of adopting and implementing the new WHO 2010 PMTCT Guidelines. These Guidelines recommend using one of two ARV prophylaxis options for HIV-infected pregnant women who do not need antiretroviral therapy (ART) for their own health. Option A consists of maternal AZT prophylaxis throughout pregnancy and delivery, complemented by daily nevirapine for the infant from birth until one week after complete cessation of breastfeeding. Option B consists of triple ART for the mother from the 14th gestational week until one week after complete cessation of breastfeeding complemented by daily nevirapine for the infant for six weeks. Both options significantly reduce the risk of mother-to-child HIV transmission (MTCT) of HIV but their advantages and disadvantages in terms of operational feasibility, safety and acceptability as well as costs have not been evaluated. The WHO guidelines state that "the choice for a preferred option should be made at a country level, after considering these advantages and disadvantages". The evidence needed to support such decision is presently lacking and critically needed for countries like Uganda that are trying to make informed choices about which option to roll out nationally. The overall goal of this operational research proposal is to compare the feasibility of delivering WHO PMTCT Options A and B in two urban Kampala hospitals and two rural hospitals in Uganda. We will enroll 600 eligible (CD4 >350) HIV- infected pregnant women into either option A or B for a total of 1,200 mother-infant pairs into the study. In each urban or rural area, one hospital will be assigned to option A and the other to Option B. In each hospital, 300 study participants will be enrolled and followed-up for 12 months post-partum. The primary aims of the study will be to compare options A and B implementation with regards to: Aim 1) maternal and infant PMTCT drug adherence measured by self report, pill counts and ARV drug detection in blood; Aim 2) maternal drug-associated severe adverse events and pregnancy outcomes; and infant safety; Aim 3) the cost-effectiveness of either option. The study will be powered to detect a difference of 10% or greater in drug adherence cumulatively and at four key time points in the cascade of PMTCT services, including the third trimester and three post-natal visits corresponding to the immunization and early infant HIV diagnosis schedules: 6 weeks post delivery, 6 months, and 12 months or at the time of breastfeeding cessation. Secondary endpoints will be to include vertical HIV transmission rates based on the presence of HIV DNA in infant blood at birth, 6 weeks of age, 6 months and 12 months of age; 12-month HIV-free survival and overall survival rates of HIV-exposed infants; and, incidence of subsequent pregnancies in the 12-month post-partum follow-up period. We will use focus group discussions and key informant interviews to assess the acceptability of either PMTCT option among HIV-infected mothers, service providers and community health leaders. The results of this study will provide critical evidence to inform operational decisions regarding the feasibility of the current WHO PMTCT recommendations in the context of resource-limited settings.