PHASE I STUDY OF PHARMACOKINETICS, SAFETY AND ACCEPTABILITY OF A SINGLE DOSE OF PRETOMANID ADDED TO AN OPTIMIZED BACKGROUND REGIMEN IN CHILDREN WITH RIFAMPICIN RESISTANT TUBERCULOSIS IMPAACT 2034

Eunice Kennedy Shriver国家儿童健康和人类发展研究所（NICHD）为国际孕产妇儿童青少年艾滋病临床试验组（IMPAACT）提供临床试验场地。IMPAACT网络及其领导小组监督所有研究、方案和临床试验的创建。IMPAACT网络是一个由机构，研究人员和其他合作者组成的合作小组，主要致力于评估艾滋病毒感染及其相关症状的潜在疗法以及婴儿，儿童，青少年和孕妇的合并感染。这包括为预防母婴传播进行艾滋病毒/艾滋病干预措施的临床试验。 IMPAACT网络的目标是开展高质量的临床试验和/或方案，以促进全球婴儿、儿童、青少年和孕妇/产后妇女艾滋病毒及其并发症的预防和治疗。本任务顺序中的IMPAACT研究议程包括四个科学具体目标，反映了关键工作领域。这些领域 艾滋病毒治疗、艾滋病毒预防、艾滋病毒治愈和艾滋病毒并发症。对于每个领域，科学委员会由特定领域的专家、研究中心调查员、社区代表和中央网络资源的代表组成，根据新兴科学以及新的想法和机会不断重新评估研究优先事项;它寻求与其他试验网络和研究实体的合作;监督基于科学优先事项的研究概念计划的制定和审查;并监察特定研究范畴内已获批准的网络研究的发展和推行情况。 1990年，NICHD开始与艾滋病临床试验组（ACTG）合作，随后于1996年与儿科艾滋病临床试验组（PACTG）合作，以扩大NICHD临床试验中心/地点的临床试验可用性。通过这一合作，IMPAACT网络得以开展临床试验，以进一步评估抗逆转录病毒治疗药物、其他针对机会性感染的疗法以及预防围产期感染的干预措施。 艾滋病毒传播。近年来，这种合作正在扩大到评估潜在的艾滋病毒治疗方法和疫苗。 在过去的35年里，NICHD和国家过敏和传染病研究所（NIAID）作为科学界的一部分，一直在进行密集的艾滋病毒研究。 在此期间，人们清楚地认识到，要成功地遏制艾滋病毒感染率的流行，并适当地对待个人的感染过程，艾滋病毒研究需要一个综合和全面的方法。此外，NICHD/NIAID和科学界的其他人在90年代中期发现，一种甚至两种不同的抗逆转录病毒药物不足以适当治疗艾滋病毒感染。因此，需要三种或更多种药物（ARV）的协同作用来有效地治疗和阻止个体艾滋病毒感染。因此，在不同的试验中开发和测试多种抗逆转录病毒药物至关重要。与此同时，一旦一种药物被开发和批准，就需要进行多项其他试验来识别它们之间的潜在协同作用。 科学界现在已经知道，实现艾滋病毒治愈（缓解）的最初尝试可能需要多种抗逆转录病毒药物的相互作用，以及感染后早期开始治疗（加上被动免疫疗法和长期抗逆转录病毒疗法的潜在使用），甚至治疗性疫苗。

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides clinical trial sites to the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). The IMPAACT network and its leadership group oversee the creation of all their studies, protocols, and clinical trials. The IMPAACT Network is a cooperative group of institutions, investigators, and other collaborators mainly focused on evaluating potential therapies for HIV infection and its related symptoms and co-infections in infants, children, adolescents, and pregnant women. This includes clinical trials of HIV/AIDS interventions for the prevention of mother to child transmission. The IMPAACT Network goal is to conduct high quality clinical trials and/or protocols that will advance the prevention and treatment of HIV and its complications for infants, children, adolescents, and pregnant/ postpartum women globally. The IMPAACT research agenda in this task order includes four scientific specific aims, which reflect the key areas of work. Those areas are HIV Treatment, HIV Prevention, HIV Cure, and HIV Complications. For each area, a Scientific Committee composed of experts in the specific field, site investigators, community representatives, and representatives of the central network resources, continually reassesses the research priorities in light of emerging science as well as new ideas and opportunities; it seeks collaboration with other trials networks and research entities; oversees the formulation and review of study concept plans based on the scientific priorities; and monitors the development and implementation of approved network studies in the specific research area. In 1990 the NICHD began collaborating with the AIDS Clinical Trials Group (ACTG) and subsequently, in 1996 with the Pediatric AIDS Clinical Trials Group (PACTG) to expand clinical trial availability at NICHD clinical trial centers/sites. This collaboration made it possible to conduct clinical trials by the IMPAACT Network to further evaluate anti-retroviral therapeutic agents, other therapies targeted at opportunistic infections, and interventions to prevent perinatal HIV transmission. In recent years, the collaboration is expanding to evaluate potential HIV cure approaches and vaccines. For the last 35 years, NICHD and the National Institute of Allergy and Infectious Diseases (NIAID), as part of the scientific community, have been conducting intense HIV research. During this time, it became clear that to be successful in the attempt to curb the HIV infection rates of the epidemic, and appropriately treat the individual infectious process, an integrated and comprehensive approach to HIV research is required. Furthermore, NICHD/NIAID and others in the scientific community found in the mid-90s that one or even two different anti-retroviral drugs (ARVs) are not sufficient to appropriately treat an individual HIV infection. Therefore, the synergy of three or more drugs (ARVs) is required to effectively treat and keep at bay an individual HIV infection. For that reason, the development and testing of multiple ARVs in different trials are essential. At the same time, as soon as a drug was developed and approved, multiple other trials were needed to discern the potential synergy between them. It is now known to the scientific community that the initial attempts to achieve an HIV Cure (remission) might require the interaction of multiple ARVs, in addition to an early start in the treatment after infection (plus the potential use of passive immunotherapy plus long-term acting anti-retroviral therapy) and even therapeutic vaccines.