STRATEGIC MANAGEMENT OF ANTIRETROVIRALS IN HIV INFECTION

HIV 感染中抗逆转录病毒药物的战略管理

• 批准号: 2828961
• 负责人: PABLO TEBAS
• 金额: $ 11.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2828961
• 关键词: AIDS therapy; HIV infections; body composition; clinical research; cytotoxic T lymphocyte; drug adverse effect; helper T lymphocyte; human subject; human therapy evaluation; mathematical model; patient care management; pharmacology; protease inhibitor; reverse transcriptase inhibitors

Over the last 2 years there have been dramatic advances in the treatment of HIV infection. The availability of protease inhibitors and non-nucleoside reverse transcriptase inhibitors allowed the development of combinations of antiretroviral drugs (HAART) that can completely block HIV viral replication. The use of highly active antiretroviral therapy has dramatically changed the morbidity and mortality rates of HIV infection and AIDS. This progress is not without problems. Protease inhibitors have major toxicities that are only partially understood. They are difficult to take requiring tight schedules and dietary restrictions and they are expensive. Better strategies in the use of these drugs are needed in order to maximize clinical benefits and improve the quality of life of patients. Given the fact that large strategic trials of many different combinations are not feasible, it is essential to determine if alternative strategic approaches can be developed. Two possible options constitute the proposed research in this grant: a)the use of statistical methods such as decision analysis to guide treatment decisions, and b) use of small pilot studies to provide basis for supporting or rejecting hypothesis that can guide strategic decisions. To accomplish these aims the investigator will: 1) Perfrom computing modeling of different strategies in the management of antiretroviral therapy in HIV infected patients using decision analysis techniques as well as Markov models; 2) Evaluate whether a fully suppressive antiretroviral regimen containing a protease inhibitor can be simplified substituting the protease inhibitor with a non-nucleoside reverse transcriptase inhibitor (NNRTI). He will also determine whether this simplification strategy has additional pathophysiologic effects correcting the metabolic abnormalities associated with protease inhibitor therapy, changing the body composition of the patients as measured by DEXA (dual energy x-ray absorptiometry) scans, or changing the distribution and absolute numbers of CD4/CD8 T memory and nave cells.

在过去两年中，艾滋病毒感染的治疗取得了巨大进展。 蛋白酶抑制剂和非核苷逆转录酶抑制剂的可用性允许开发可以完全阻断HIV病毒复制的抗逆转录病毒药物（HAART）的组合。 高效抗逆转录病毒疗法的使用极大地改变了艾滋病毒感染和艾滋病的发病率和死亡率。这一进展并非没有问题。 蛋白酶抑制剂具有仅部分了解的主要毒性。 他们很难采取需要紧张的时间表和饮食限制，他们是昂贵的。 需要更好的策略来使用这些药物，以最大限度地提高临床效益和改善患者的生活质量。鉴于许多不同组合的大规模战略试验是不可行的，确定是否可以开发替代战略方法至关重要。 两种可能的选择构成了本补助金中拟议的研究：a）使用统计方法，如决策分析，以指导治疗决策，以及B）使用小型试点研究，为支持或拒绝可以指导战略决策的假设提供基础。为了实现这些目标，研究者将：1）使用决策分析技术以及马尔可夫模型，对HIV感染患者抗逆转录病毒治疗中的不同策略进行计算建模; 2）评价是否可以简化包含蛋白酶抑制剂的完全抑制性抗逆转录病毒治疗方案，用非核苷逆转录酶抑制剂（NNRTI）替代蛋白酶抑制剂。他还将确定这种简化策略是否具有额外的病理生理作用，纠正与蛋白酶抑制剂治疗相关的代谢异常，改变患者的身体组成（通过DEXA（双能X射线吸收测定法）扫描测量），或改变CD 4/CD 8 T记忆和NA的分布和绝对数量。ve细胞。