RESPIRATORY DISEASES/BSI STUDY

呼吸系统疾病/BSI 研究

• 批准号: 6388276
• 负责人: SHAHIN LOCKMAN
• 金额: $ 12.62万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-11 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6388276
• 关键词: AIDS education /prevention; AIDS therapy; Africa; African; HIV infections; breast feeding; clinical research; diet route /schedule; human immunodeficiency virus 1; human pregnant subject; human subject; human therapy evaluation; infant human (0-1 year); nevirapine; respiratory disorder; vertical transmission; zidovudine

DESCRIPTION: (Adapted from the application) Shahin Lockman, M.D. has completed an Infectious Diseases fellowship at Massachusetts General/Brigham and Women's Hospitals in Boston and a two-year Epidemic Intelligence Service program at the Centers for Disease Control Division of Tuberculosis (TB) Elimination. In this latter capacity she helped to plan and execute multiple studies pertaining to the epidemiology of TB and HIV in Botswana and Estonia. She will work with Dr. Max Essex on clinical trials studying approaches to perinatal HIV transmission prevention in Botswana, as well as studies of other aspects of HIV epidemiology and infant infectious disease morbidity and mortality. The candidate plans to pursue an independent career in HIV and TB epidemiology and clinical trials. HIV-I prevalence among women of child-bearing age in Botswana is 28-43%, and greater than 33% of infants born to these women are likely to be infected. Seven to 22% of HIV-infected women may transmit HIV to their infants via breast milk; breast-feeding is widely practiced throughout sub-Saharan Africa. The critical question of rates of overall mortality and infectious disease morbidity among infants of HIV-positive mothers who are breast-fed while receiving prophylactic antiretrovirals versus those who are formula-fed has not been answered. Acute respiratory infection is a leading cause of Infant morbidity and mortality in the developing world, the etiology and outcome of respiratory disease and bloodstream infection in HIV-infected infants in sub- Saharan Africa have not been evaluated prospectively, nor have they been compared between breast- and formula-feeding infants in this setting. Answers to these questions would be of value to clinicians and to national health policy-makers. Finally, the efficacy and safety of antenatal/intrapartum ZDV versus the same regimen plus short-course nevirapine have not been studied in pregnant HIV-infected mothers and their infants. The primary study objectives are to determine the efficacy and safety of ZDV given for 6 months to infants born to HIV-infected mothers for reducing HIV-I subtype C transmission by breast-feeding compared with formula-feeding, and to study the efficacy of ZDV versus ZDV plus short-course nevirapine in preventing mother-to-infant HIV transmission. Other objectives Include evaluating (a) etiology and outcome of infant respiratory disease and bloodstream infection in Botswana, and ascertaining any protective effect of breast milk on respiratory disease morbidity and mortality, (b) decision analysis of the most efficacious feeding strategy for infants of HIV-positive mothers, comparing breast-feeding, with prophylactic infant ZDV and formula-feeding and (c) HIV-I viral phenotypes and genotypes/drug resistance mutations in HIV-infected infants treated with ZDV. The candidate will be a principal investigator on (a) and (b), and will assist with achieving all other study objectives. The study will be carried out in 3 towns in southeast Botswana as a collaborative effort between the Harvard AIDS Institute and the AIDS/STD Unit of Botswana. Baseline rates of transmission are being ascertained from HIV-infected mothers (and their infants) who have already delivered. The proposed intervention will involve HIV-infected consenting pregnant women, and will consist of giving: 1) all women ZDV from 34 weeks of gestation to one week post-partum- one half of the mothers and infants will each receive one dose of intrapartum/post-partum nevirapine, and the other half will receive placebo, and 2) one half of infants will be randomized to formula-feeding and the other half to breast-feeding plus ZDV for 6 months. In addition, Dr. Lockman will compare the rates, etiologies, and outcomes of respiratory disease, bloodstream infection, and nasopharyngeal colonization with pathogens between the breast-feeding and formula-feeding infants, stratified by HIV status, and will perform a decision analysis evaluating optimal infant feeding strategy in Botswana and in similar settings with high HIV prevalence and relatively high infant mortality rates from other infectious diseases.

描述：（改编自申请）Shahin Lockman，医学博士已完成 马萨诸塞州总医院/布莱根妇女医院传染病奖学金 波士顿的医院和位于波士顿的为期两年的流行病情报服务计划 疾病控制中心结核病 (TB) 消除司。在 她帮助规划和执行了多项研究 有关博茨瓦纳和爱沙尼亚结核病和艾滋病毒的流行病学。她会 与 Max Essex 博士合作进行临床试验，研究围产期方法 博茨瓦纳艾滋病毒传播预防及其他方面的研究 HIV流行病学和婴儿传染病发病率和死亡率。这 候选人计划在艾滋病毒和结核病流行病学领域追求独立的职业生涯，并且 临床试验。 博茨瓦纳育龄妇女的 HIV-I 感染率为 28-43%， 这些妇女所生的婴儿中有超过 33% 可能被感染。 7% 至 22% 的 HIV 感染妇女可能通过以下途径将 HIV 传染给婴儿： 母乳；母乳喂养在撒哈拉以南非洲地区广泛实行。 总体死亡率和传染病率的关键问题 艾滋病毒呈阳性的母亲在母乳喂养期间所生婴儿的发病率 与接受配方奶喂养的人相比，接受预防性抗逆转录病毒药物的人 没有得到答复。急性呼吸道感染是婴儿感染的主要原因 发展中国家的发病率和死亡率、病因和结果 亚裔艾滋病毒感染婴儿的呼吸道疾病和血流感染 撒哈拉非洲尚未进行前瞻性评估，也未进行过评估 在这种情况下，对母乳喂养和配方奶喂养的婴儿进行比较。答案 这些问题对临床医生和国民健康都很有价值 政策制定者。最后，产前/产时 ZDV 的有效性和安全性 尚未对相同方案加短程奈韦拉平进行比较 感染艾滋病毒的孕妇及其婴儿。 主要研究目标是确定 ZDV 的有效性和安全性 给感染 HIV 的母亲所生的婴儿服用 6 个月，以减少 HIV-I 与配方奶喂养相比，母乳喂养导致的 C 亚型传播 研究 ZDV 与 ZDV 加短程奈韦拉平治疗的疗效 预防艾滋病毒母婴传播。 其他目标包括 评估 (a) 婴儿呼吸道疾病的病因和结果，以及 博茨瓦纳的血流感染，并确定其任何保护作用 母乳对呼吸道疾病发病率和死亡率的影响，(b) 决定 HIV阳性婴儿最有效喂养策略分析 母亲们将母乳喂养与预防性婴儿 ZDV 进行比较 配方奶喂养和(c) HIV-1病毒表型和基因型/耐药性 接受 ZDV 治疗的 HIV 感染婴儿的突变。 候选人将是 (a) 和 (b) 的首席研究员，并将协助实现所有目标 其他学习目标。该研究将在东南部3个城镇进行 博茨瓦纳是哈佛艾滋病研究所和 博茨瓦纳艾滋病/性传播疾病部门。 基线传输率正在 从已感染艾滋病毒的母亲（及其婴儿）中确定 发表。拟议的干预措施将涉及艾滋病毒感染者的同意 孕妇，包括给予： 1) 所有女性从怀孕 34 周开始注射 ZDV 妊娠期至产后一周——一半的母亲和婴儿会 每人接受一剂产时/产后奈韦拉平，另一人接受一剂产时/产后奈韦拉平治疗 一半将接受安慰剂，并且 2) 一半婴儿将被随机分配到 配方奶喂养，另一半母乳喂养加ZDV 6个月。在 此外，洛克曼博士将比较以下疾病的发生率、病因和结果： 呼吸道疾病、血流感染和鼻咽定植 母乳喂养和配方奶喂养的婴儿之间存在病原体， 按艾滋病毒状况分层，并将进行决策分析评估 博茨瓦纳和类似环境下的最佳婴儿喂养策略 艾滋病毒感染率和其他地区相对较高的婴儿死亡率 传染病。