Optimizing HIV Care in Less Developed Countries

描述(申请人提供)：过去几年，在向发展中国家的艾滋病毒感染者提供治疗和护理方面取得了重大进展。然而，在最佳治疗策略、二线和三线抗逆转录病毒治疗的费用以及扩大护理的影响方面，仍然存在很大的不确定性。随着艾滋病毒疫情的持续增长，这些问题需要进行批判性分析。2004年，NIAID授予我们的研究小组资金，用于开发“预防艾滋病并发症的成本效益(CEPAC)国际”模型，这是一种对南非、科特迪瓦和印度艾滋病毒疾病的自然历史、临床管理、结果和成本进行计算机模拟的模型。目前的项目已经发表了16篇出版物，包括一篇被广泛引用的《新英格兰医学杂志》的文章，以及在最初的3年里提交或起草的9篇手稿。在这一竞争的延续中，我们请求支持开发第二代CEPAC-国际模式。这一新模型将反映对艾滋病毒和艾滋病流行病学、治疗效果、对结核病传播的影响以及护理成本效益的最新了解。当前提案的三个具体目标是：1)完善CEPAC-国际模式对关键患者和人群水平影响的描述。这将包括时间错开的多个入境队列、艾滋病毒人与人之间的传播和结核病传播、与抗逆转录病毒相关的长期毒性和共病，以及完善抗逆转录病毒耐药性的方法。2)预测发展中国家艾滋病毒护理的不同患者水平治疗战略的临床结果、成本和成本效益；以及3)确定发展中国家人口水平的最佳艾滋病毒和艾滋病治疗和预防战略。聚集在一起的研究团队在出版和传播研究结果方面有着广泛的记录，这些发现为美国和国际上艾滋病毒护理和实践指南制定的优先事项提供了信息。为了增强团队的建模能力，团队中增加了在艾滋病毒/结核病合并感染、传播动力学以及传染病建模方面经验丰富的熟练调查人员。通过继续这个多学科小组已经取得的重大进展，并实现上述具体目标，拟议的研究将解决发展中国家的提供者和政策制定者在未来几年将面临的最关键的艾滋病毒临床政策和成本效益问题。公共卫生相关性尽管最近全球在向发展中国家提供艾滋病毒治疗和护理方面取得了进展，但在充分实施这些计划和了解世界各地不同艾滋病毒护理战略的临床结果和成本效益方面仍然存在重大挑战。CEPAC-国际模式提供了一种廉价但广泛适用的方法来研究艾滋病毒干预措施，预测其结果，并强调未来研究的重要领域。我们计划的灵活性使我们的团队能够从多个角度调查问题，通过大规模临床试验提供对可能无法在现实生活环境中测试的场景的洞察。

DESCRIPTION (provided by applicant): The past several years have seen major progress in the delivery of treatment and care to HIV-infected people in the developing world. However, substantial uncertainty persists regarding optimal treatment strategies, the cost of second- and third-line antiretroviral treatment, and the impact of expanded care. As the HIV epidemic continues to grow, these problems require critical analysis. In 2004, NIAID awarded our research group funding to develop the "Cost-effectiveness of Preventing AlDS Complications (CEPAC) International" Model, a computer simulation of the natural history, clinical management, outcomes, and costs of HIV disease in South Africa, Cote d'lvoire, and India. The current project has produced 16 publications, including a widely cited New England Journal of Medicine article, and another 9 submitted or draft manuscripts in its first 3 years. In this competing continuation, we request support to develop a 2nd generation CEPAC-International Model. This new model will reflect the most current understanding of HIV and AlDS epidemiology, treatment efficacy, impact on TB transmission and cost-effectiveness of care. The three specific aims of the current proposal are: 1) To refine the CEPAC-International Model's portrayal of critical patient- and population-level effects. This will include multiple entry cohorts staggered in time, person-to-person HIV transmission and TB transmission, long-term ART-related toxicities and co-morbidities, and to refine the approach to antiretroviral drug resistance. 2) To project clinical outcomes, cost, and cost-effectiveness of different patient-level treatment strategies for HIV care in developing countries; and 3) To identify optimal population-level HIV and AIDS treatment and prevention strategies in developing countries. The assembled research team has an extensive record of publishing and disseminating findings that inform priority setting in HIV care and practice guideline development, in the US and internationally. To augment the team's modeling capacity, skilled investigators with experience in HIV/TB co-infection, transmission dynamics as well as infectious disease modeling have been added to the team. By continuing the major progress already made by this multidisciplinary team, and accomplishing the specific aims described above, the proposed studies will address the most crucial HIV clinical policy and cost-effectiveness questions that will face providers and policy-makers in developing countries over the next several years. PUBLIC HEALTH RELEVANCE Despite recent progress globally to deliver HIV treatment and care to developing countries, major challenges remain in fully implementing these programs and understanding the clinical outcomes and cost-effectiveness of different strategies for HIV care worldwide. The CEPAC-International Model provides an inexpensive yet broadly applicable way of studying HIV interventions, projecting their outcomes, and highlighting important areas for future research. The flexibility of our program allows our team to investigate problems from several angles, providing insight into scenarios that may not be feasible to test in real-life settings through large-scale clinical trials.