Point-of-care virologic testing to improve outcomes of HIV-infected children

描述（由申请人提供）：尽管我们尽最大努力推出母婴艾滋病毒预防服务，但赞比亚等发展中国家的许多儿童仍无法逃脱感染。幸运的是，现在许多地方都可以使用挽救生命的抗逆转录病毒疗法，但为了使其发挥作用，必须识别受感染的新生儿并立即开始治疗。婴儿艾滋病毒感染的诊断是这一过程的主要障碍。与成人的艾滋病毒检测不同，婴儿诊断需要特殊的实验室设备和只有先进实验室才有的人员。因此，大多数儿童要么根本无法获得艾滋病毒诊断，要么必须等待数周才能收到检测结果。在赞比亚，与该地区的许多国家一样，超过一半接受检测并发现感染的新生儿从未真正开始治疗。剑桥大学开发了一种名为“SAMBA”的新型即时护理（POC）测试，可以通过检测血液中的艾滋病毒遗传物质来诊断婴儿艾滋病毒感染。 SAMBA 专为发展中国家环境设计，两小时内即可得出结果。该测试有两种版本：定性测试（用于婴儿诊断）和半定量测试（用于治疗监测）。该提案描述了一项 SAMBA POC 病毒学测试的整群随机试验，旨在改善赞比亚艾滋病毒感染儿童的治疗结果。 POC 技术将应用于初级保健场所，并发挥两项功能：(1) 为感染 HIV 的母亲所生的婴儿在出生后 6 周内提供当天的早期婴儿 HIV 诊断；(2) 对接受抗逆转录病毒治疗的儿童进行治疗监测。十二家机构将参加试验。一半的站点将被随机分配以实施 POC 技术，另一半将采用当前的护理标准——婴儿诊断在场外进行，治疗监测主要基于临床评估。该试验的主要结果将是每个研究组中感染艾滋病毒的儿童在初次诊断 18 个月后仍存活、接受护理且血液中没有艾滋病毒循环的比例（治疗成功的指标）。该研究将由赞比亚传染病研究中心（CIDRZ）进行。 CIDRZ 成立于 2001 年，由提出这项研究的团队领导，在 NIH 资助的研究和 PEPFAR 资助的服务实施方面拥有丰富的经验。 公共卫生相关性：尽管预防艾滋病毒母婴传播的干预措施越来越多，但赞比亚等发展中国家的许多儿童仍无法逃脱感染。识别受感染的新生儿并立即开始抗逆转录病毒治疗对生存具有深远的影响。该提案概述了一项临床试验，旨在测试新的护理点诊断技术在识别受感染儿童方面的现场有效性 并立即开始对他们进行挽救生命的抗逆转录病毒治疗。

DESCRIPTION (provided by applicant): Despite our best efforts to roll out mother-to-child HIV prevention services, many children in developing nations such as Zambia do not escape infection. Fortunately, life-saving antiretroviral therapy is now available in many settings, but i order for it to work, infected newborns must be identified and treatment started immediately. Diagnosis of infant HIV infection represents a major hurdle to this process. Unlike HIV testing in adults, infant diagnosis requires special laboratory equipment and personnel available only in sophisticated laboratories. As a result, most children either have no access to HIV diagnosis at all or must wait for weeks to receive their test result. In Zambia - as in many countries in the region - more than half of newborns who are tested and found to be infected never actually start treatment. The University of Cambridge has developed a new point-of-care (POC) test called "SAMBA" that can diagnose infant HIV infection by detecting HIV genetic material in the blood. Designed specifically for developing world settings, SAMBA results are ready in two hours. Two versions of the test are available, a qualitative test (for infant diagnosis) and a semi-quantitatie test (for treatment monitoring). This proposal describes a cluster-randomized trial of the SAMBA POC virologic test to improve outcomes of HIV-infected children in Zambia. The POC technology will be placed in primary care sites and serve two functions: (1) provision of same-day, early infant HIV diagnosis at 6 weeks of life for infants born to HIV-infected mothers, and (2) treatment monitoring of children on antiretroviral therapy. Twelve facilities will participate n the trial. Half of the sites will be randomly assigned to implement the POC technology and the other half will employ the current standard of care - where infant diagnosis is performed off site and treatment monitoring is based primarily upon clinical assessment. The trial's primary outcome will be the proportion of HIV-infected children in each study arm who remain alive, in care, and with no HIV circulating in their bloodstream (an indicator of treatment success) 18 months after their initial diagnosis. The study will be conducted by the Centre for Infectious Disease Research in Zambia (CIDRZ). Established in 2001, and led by the team proposing this study, CIDRZ has substantial experience with both NIH-sponsored research and PEPFAR-sponsored service implementation. PUBLIC HEALTH RELEVANCE: Although interventions to prevent mother-to-child HIV transmission are becoming increasingly available, many children in developing nations such as Zambia do not escape infection. Identifying infected newborns and starting immediate antiretroviral therapy has a profound survival effect. This proposal outlines a clinical trial to tst the field effectiveness of a new point- of-care diagnostic technology to identify infected children and start them immediately on life- saving antiretroviral therapy.