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首页> 外文期刊>Computer Methods and Programs in Biomedicine: An International Journal Devoted to the Development, Implementation and Exchange of Computing Methodology and Software Systems in Biomedical Research and Medical Practice >Computer simulation of structured treatment interruption for HIV infection.
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Computer simulation of structured treatment interruption for HIV infection.

机译：针对HIV感染的结构化治疗中断的计算机模拟。

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The use of highly active antiretroviral therapy (HAART) for suppression of measurable levels of virus in the body has greatly contributed to restoration and preservation of the immune system in HIV positive patients. However, short and long term problems associated with HAART have led to proposals for alternative treatment strategies for controlling HIV infection. In particular, structured treatment interruptions (STIs) that consist of therapy withdrawal and re-initiation according to specific criteria have been considered. The aim of these STIs was one or both of: (i) to stimulate the immune system to react to HIV, (ii) to allow re-emergence of wild-type virus and thereby reduce problems of drug resistance. However, a number of clinical trials of STIs have shown adverse outcomes for patients under discontinuous therapy, including serious health risks associated with treatment interruptions. In this paper we consider in some detail two of the larger clinical studies, namely, (a) strategies for management of anti-retroviral therapy (SMART); (b) Staccato study. For each of these studies we perform computer simulations of the treatment strategies. These simulations suggest several underlying reasons for the adverse outcomes during treatment interruption. In particular, HIV infection exhibits rapid dynamic load changes, and therefore measurement based treatment regimes need to be carefully designed to avoid large transients in healthy CD4+ T cell count. Furthermore, repeated treatment interruptions may accelerate the emergence of resistant mutant virus and may increase the infection of long term reservoirs such as macrophages which will accelerate progression to AIDS.
机译：使用高效抗逆转录病毒疗法（HAART）抑制体内可测量的病毒水平，极大地有助于恢复和保存HIV阳性患者的免疫系统。但是，与HAART相关的短期和长期问题已提出了控制HIV感染的替代治疗策略的建议。特别是，已经考虑了结构化的治疗中断（STIs），包括根据特定标准的治疗退出和重新启动。这些性传播感染的目的是以下一种或两种：（i）刺激免疫系统对HIV反应;（ii）允许野生型病毒再次出现，从而减少耐药性问题。但是，许多性传播感染的临床试验显示，不连续治疗的患者预后不良，包括与治疗中断相关的严重健康风险。在本文中，我们更详细地考虑了两项较大的临床研究，即（a）抗逆转录病毒疗法（SMART）的管理策略; （b）断音研究。对于这些研究中的每一项，我们都对治疗策略进行计算机模拟。这些模拟提示了治疗中断期间不良后果的几种潜在原因。特别是，HIV感染表现出快速的动态负荷变化，因此需要仔细设计基于测量的治疗方案，以避免健康的CD4 + T细胞计数出现较大的瞬变。此外，反复的治疗中断可能会加速抗药性突变病毒的出现，并可能增加长期储存库（如巨噬细胞）的感染，这将加速艾滋病的发展。

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